更新情報
PDQ®日本語版の更新情報

PDQ®（Physician Data Query）

米国国立がん研究所（NCI）の
PDQ®トップページ

医療専門家向け Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (PDQ®)

ご利用について

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of ovarian epithelial, fallopian tube, and primary peritoneal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

CONTENTS 全て開く全て閉じる

General Information About Ovarian Epithelial Cancer, Fallopian Tube Cancer (FTC), and Primary Peritoneal Cancer (PPC)

This PDQ summary addresses the staging and treatment of ovarian epithelial cancer, fallopian tube cancer (FTC), and primary peritoneal cancer (PPC).

Regardless of the site of origin, the hallmark of these cancers is their early peritoneal spread of metastases. The inclusion of FTC and PPC within the ovarian epithelial cancer designation is generally accepted because of much evidence that points to a common Müllerian epithelium derivation and similar management of these three neoplasms. The hypothesis that many high-grade serous ovarian cancers (the most common histologic subtype) may arise from precursor lesions that originate in the fimbriae of the fallopian tubes has been supported by findings from risk-reducing surgeries in healthy women with BRCA1 or BRCA2 mutations.[ 1 ] In addition, histologically similar cancers diagnosed as primary peritoneal carcinomas share molecular findings, such as loss or inactivation of the tumor-suppressor p53 and BRCA1 or BRCA2 proteins.[ 2 ] Therefore, high-grade serous adenocarcinomas arising from the fallopian tube and elsewhere in the peritoneal cavity, together with most ovarian epithelial cancers, represent extrauterine adenocarcinomas of Müllerian epithelial origin and are staged and treated similarly to ovarian cancer. Since 2000, FTC and PPC have usually been included in ovarian cancer clinical trials.[ 3 ]

Clear cell and endometrioid ovarian cancers that are linked to endometriosis have different gene-expression signatures, as do mucinous subtypes.[ 2 ]

Stromal and germ cell tumors are relatively uncommon and comprise fewer than 10% of cases. (Refer to the PDQ summaries on Ovarian Germ Cell Tumors Treatment and Ovarian Low Malignant Potential Tumors Treatment for more information.)

Incidence and Mortality

Epithelial carcinoma of the ovary is one of the most common gynecologic malignancies, with 50% of all cases occurring in women older than 65 years. It is the fifth most frequent cause of cancer death in women.[ 4 ]

Estimated new cases and deaths from ovarian cancer in the United States in 2019:[ 5 ]

Anatomy

The fimbriated ends of the fallopian tubes are in close apposition to the ovaries and in the peritoneal space, as opposed to the corpus uteri (body of the uterus) that is located under a layer of peritoneum.

Anatomy of the female reproductive system; drawing shows the uterus, myometrium (muscular outer layer of the uterus), endometrium (inner lining of the uterus), ovaries, fallopian tubes, cervix, and vagina.

画像を拡大する

Normal female reproductive system anatomy.

Risk Factors

Increasing age is the most important risk factor for most cancers. Other risk factors for ovarian (epithelial) cancer include the following:

Family history and genetic alterations

The most important risk factor for ovarian cancer is a history of ovarian cancer in a first-degree relative (mother, daughter, or sister). Approximately 20% of ovarian cancers are familial, and although most of these are linked to mutations in either the BRCA1 or BRCA2 gene, several other genes have been implicated.[ 19 ][ 20 ] The risk is highest in women who have two or more first-degree relatives with ovarian cancer.[ 21 ] The risk is somewhat less for women who have one first-degree relative and one second-degree relative (grandmother or aunt) with ovarian cancer.

In most families affected with breast and ovarian cancer syndrome or site-specific ovarian cancer, genetic linkage to the BRCA1 locus on chromosome 17q21 has been identified.[ 22 ][ 23 ][ 24 ] BRCA2, also responsible for some instances of inherited ovarian and breast cancer, has been mapped by genetic linkage to chromosome 13q12.[ 25 ]

The lifetime risk for developing ovarian cancer in patients harboring germline mutations in BRCA1 is substantially increased over that of the general population.[ 26 ][ 27 ] Two retrospective studies of patients with germline mutations in BRCA1 suggest that the women in these studies have improved survival compared with BRCA1 mutation–negative women.[ 28 ][ 29 ][Level of evidence: 3iiiA] Most women with a BRCA1 mutation probably have family members with a history of ovarian and/or breast cancer; therefore, the women in these studies may have been more vigilant and inclined to participate in cancer screening programs that may have led to earlier detection.

For women at increased risk, prophylactic oophorectomy may be considered after age 35 years if childbearing is complete. In a family-based study among 551 women with BRCA1 or BRCA2 mutations, of the 259 women who had undergone bilateral prophylactic oophorectomy, 2 (0.8%) developed subsequent papillary serous peritoneal carcinoma, and 6 (2.8%) had stage I ovarian cancer at the time of surgery. Of the 292 matched controls, 20% who did not have prophylactic surgery developed ovarian cancer. Prophylactic surgery was associated with a reduction in the risk of ovarian cancer that exceeded 90% (relative risk, 0.04; 95% confidence interval, 0.01–0.16), with an average follow-up of 9 years;[ 30 ] however, family-based studies may be associated with biases resulting from case selection and other factors that influence the estimate of benefit.[ 31 ] After a prophylactic oophorectomy, a small percentage of women may develop a primary peritoneal carcinoma that is similar in appearance to ovarian cancer.[ 32 ] (Refer to the Description of the Evidence section in the PDQ summary on Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Prevention for more information.)

(Refer to the Clinical Management of BRCA Mutation Carriers section in the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information.)

Clinical Presentation

Ovarian, fallopian tube, or peritoneal cancer may not cause early signs or symptoms. When signs or symptoms do appear, the cancer is often advanced. Signs and symptoms include the following:

These symptoms often go unrecognized, leading to delays in diagnosis. Efforts have been made to enhance physician and patient awareness of the occurrence of these nonspecific symptoms.[ 33 ][ 34 ][ 35 ][ 36 ][ 37 ]

Screening procedures such as gynecologic assessment, vaginal ultrasound, and cancer antigen 125 (CA-125) assay have had low predictive value in detecting ovarian cancer in women without special risk factors.[ 38 ][ 39 ] As a result of these confounding factors, annual mortality in ovarian cancer is approximately 65% of the incidence rate.

Most patients with ovarian cancer have widespread disease at presentation. Early peritoneal spread of the most common subtype of high-grade serous cancers may relate to serous cancers starting in the fimbriae of the fallopian tubes or in the peritoneum, readily explaining why such cancers are detected at an advanced stage. Conversely, high-grade serous cancers are underrepresented among stage I cancers of the ovary. Other types of ovarian cancers are, in fact, overrepresented in cancers detected in stages I and II. This type of ovarian cancer usually spreads via local shedding into the peritoneal cavity followed by implantation on the peritoneum and via local invasion of bowel and bladder. The incidence of positive nodes at primary surgery has been reported to be as high as 24% in patients with stage I disease, 50% in patients with stage II disease, 74% in patients with stage III disease, and 73% in patients with stage IV disease. The pelvic nodes were involved as often as the para-aortic nodes.[ 40 ] Tumor cells may also block diaphragmatic lymphatics. The resulting impairment of lymphatic drainage of the peritoneum is thought to play a role in development of ascites in ovarian cancer. Transdiaphragmatic spread to the pleura is common.

Diagnostic and Staging Evaluation

The following tests and procedures may be used in the diagnosis and staging of ovarian epithelial, fallopian tube, or primary peritoneal cancer:

CA-125 levels can be elevated in other malignancies and benign gynecologic problems such as endometriosis. CA-125 levels and histology are used to diagnose epithelial ovarian cancer.[ 41 ][ 42 ]

Prognostic Factors

Prognosis for patients with ovarian cancer is influenced by multiple factors. Multivariate analyses suggest that the most important favorable prognostic factors include the following:[ 43 ][ 44 ][ 45 ][ 46 ][ 47 ]

For patients with stage I disease, the most important prognostic factor associated with relapse is grade, followed by dense adherence and large-volume ascites.[ 48 ] Stage I tumors have a high proportion of low-grade serous cancers. These cancers have a derivation distinctly different from that of high-grade serous cancers, which usually present in stages III and IV. Many high-grade serous cancers originate in the fallopian tube and other areas of extrauterine Müllerian epithelial origin.

If the tumor is grade III, densely adherent, or stage IC, the chance of relapse and death from ovarian cancer is as much as 30%.[ 48 ][ 49 ][ 50 ][ 51 ]

The use of DNA flow cytometric analysis of tumors from stage I and stage IIA patients may identify a group of high-risk patients.[ 52 ] Patients with clear cell histology appear to have a worse prognosis.[ 53 ] Patients with a significant component of transitional cell carcinoma appear to have a better prognosis.[ 54 ]

Case-control studies suggest that BRCA1 and BRCA2 mutation carriers have improved responses to chemotherapy when compared with patients with sporadic epithelial ovarian cancer. This may be the result of a deficient homologous DNA repair mechanism in these tumors, which leads to increased sensitivity to chemotherapy agents.[ 55 ][ 56 ]

Follow-up

Because of the low specificity and sensitivity of the CA-125 assay, serial CA-125 monitoring of patients undergoing treatment for recurrence may be useful. However, whether that confers a net benefit has not yet been determined. There is little guidance about how patients should be followed up after initial induction therapy, and neither early detection by imaging or by CA-125 elevation has been shown to alter outcomes.[ 57 ] (Refer to the Recurrent or Persistent Ovarian Epithelial, FTC, and PPC Treatment section of this summary for more information.)

Related Summaries

Other PDQ summaries containing information related to ovarian epithelial, fallopian tube, and primary peritoneal cancer include the following:

参考文献
  1. Levanon K, Crum C, Drapkin R: New insights into the pathogenesis of serous ovarian cancer and its clinical impact. J Clin Oncol 26 (32): 5284-93, 2008.[PUBMED Abstract]
  2. Birrer MJ: The origin of ovarian cancer—is it getting clearer? N Engl J Med 363 (16): 1574-5, 2010.[PUBMED Abstract]
  3. Dubeau L, Drapkin R: Coming into focus: the nonovarian origins of ovarian cancer. Ann Oncol 24 (Suppl 8): viii28-viii35, 2013.[PUBMED Abstract]
  4. Yancik R: Ovarian cancer. Age contrasts in incidence, histology, disease stage at diagnosis, and mortality. Cancer 71 (2 Suppl): 517-23, 1993.[PUBMED Abstract]
  5. American Cancer Society: Cancer Facts and Figures 2019. Atlanta, Ga: American Cancer Society, 2019. Available online. Last accessed December 12, 2019.[PUBMED Abstract]
  6. Bolton KL, Ganda C, Berchuck A, et al.: Role of common genetic variants in ovarian cancer susceptibility and outcome: progress to date from the Ovarian Cancer Association Consortium (OCAC). J Intern Med 271 (4): 366-78, 2012.[PUBMED Abstract]
  7. Weissman SM, Weiss SM, Newlin AC: Genetic testing by cancer site: ovary. Cancer J 18 (4): 320-7, 2012 Jul-Aug.[PUBMED Abstract]
  8. Hunn J, Rodriguez GC: Ovarian cancer: etiology, risk factors, and epidemiology. Clin Obstet Gynecol 55 (1): 3-23, 2012.[PUBMED Abstract]
  9. Pal T, Akbari MR, Sun P, et al.: Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer. Br J Cancer 107 (10): 1783-90, 2012.[PUBMED Abstract]
  10. Gayther SA, Pharoah PD: The inherited genetics of ovarian and endometrial cancer. Curr Opin Genet Dev 20 (3): 231-8, 2010.[PUBMED Abstract]
  11. Poole EM, Lin WT, Kvaskoff M, et al.: Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of U.S. nurses. Cancer Causes Control 28 (5): 437-445, 2017.[PUBMED Abstract]
  12. Pearce CL, Templeman C, Rossing MA, et al.: Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 13 (4): 385-94, 2012.[PUBMED Abstract]
  13. Mogensen JB, Kjær SK, Mellemkjær L, et al.: Endometriosis and risks for ovarian, endometrial and breast cancers: A nationwide cohort study. Gynecol Oncol 143 (1): 87-92, 2016.[PUBMED Abstract]
  14. Lacey JV, Brinton LA, Leitzmann MF, et al.: Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst 98 (19): 1397-405, 2006.[PUBMED Abstract]
  15. Trabert B, Wentzensen N, Yang HP, et al.: Ovarian cancer and menopausal hormone therapy in the NIH-AARP diet and health study. Br J Cancer 107 (7): 1181-7, 2012.[PUBMED Abstract]
  16. Engeland A, Tretli S, Bjørge T: Height, body mass index, and ovarian cancer: a follow-up of 1.1 million Norwegian women. J Natl Cancer Inst 95 (16): 1244-8, 2003.[PUBMED Abstract]
  17. Lahmann PH, Cust AE, Friedenreich CM, et al.: Anthropometric measures and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 126 (10): 2404-15, 2010.[PUBMED Abstract]
  18. Collaborative Group on Epidemiological Studies of Ovarian Cancer: Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies. PLoS Med 9 (4): e1001200, 2012.[PUBMED Abstract]
  19. Lynch HT, Watson P, Lynch JF, et al.: Hereditary ovarian cancer. Heterogeneity in age at onset. Cancer 71 (2 Suppl): 573-81, 1993.[PUBMED Abstract]
  20. Pennington KP, Swisher EM: Hereditary ovarian cancer: beyond the usual suspects. Gynecol Oncol 124 (2): 347-53, 2012.[PUBMED Abstract]
  21. Piver MS, Goldberg JM, Tsukada Y, et al.: Characteristics of familial ovarian cancer: a report of the first 1,000 families in the Gilda Radner Familial Ovarian Cancer Registry. Eur J Gynaecol Oncol 17 (3): 169-76, 1996.[PUBMED Abstract]
  22. Miki Y, Swensen J, Shattuck-Eidens D, et al.: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266 (5182): 66-71, 1994.[PUBMED Abstract]
  23. Easton DF, Bishop DT, Ford D, et al.: Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet 52 (4): 678-701, 1993.[PUBMED Abstract]
  24. Steichen-Gersdorf E, Gallion HH, Ford D, et al.: Familial site-specific ovarian cancer is linked to BRCA1 on 17q12-21. Am J Hum Genet 55 (5): 870-5, 1994.[PUBMED Abstract]
  25. Wooster R, Neuhausen SL, Mangion J, et al.: Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 265 (5181): 2088-90, 1994.[PUBMED Abstract]
  26. Easton DF, Ford D, Bishop DT: Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 56 (1): 265-71, 1995.[PUBMED Abstract]
  27. Struewing JP, Hartge P, Wacholder S, et al.: The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336 (20): 1401-8, 1997.[PUBMED Abstract]
  28. Rubin SC, Benjamin I, Behbakht K, et al.: Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1. N Engl J Med 335 (19): 1413-6, 1996.[PUBMED Abstract]
  29. Aida H, Takakuwa K, Nagata H, et al.: Clinical features of ovarian cancer in Japanese women with germ-line mutations of BRCA1. Clin Cancer Res 4 (1): 235-40, 1998.[PUBMED Abstract]
  30. Rebbeck TR, Lynch HT, Neuhausen SL, et al.: Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346 (21): 1616-22, 2002.[PUBMED Abstract]
  31. Klaren HM, van't Veer LJ, van Leeuwen FE, et al.: Potential for bias in studies on efficacy of prophylactic surgery for BRCA1 and BRCA2 mutation. J Natl Cancer Inst 95 (13): 941-7, 2003.[PUBMED Abstract]
  32. Piver MS, Jishi MF, Tsukada Y, et al.: Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer. A report of the Gilda Radner Familial Ovarian Cancer Registry. Cancer 71 (9): 2751-5, 1993.[PUBMED Abstract]
  33. Goff BA, Mandel L, Muntz HG, et al.: Ovarian carcinoma diagnosis. Cancer 89 (10): 2068-75, 2000.[PUBMED Abstract]
  34. Friedman GD, Skilling JS, Udaltsova NV, et al.: Early symptoms of ovarian cancer: a case-control study without recall bias. Fam Pract 22 (5): 548-53, 2005.[PUBMED Abstract]
  35. Smith LH, Morris CR, Yasmeen S, et al.: Ovarian cancer: can we make the clinical diagnosis earlier? Cancer 104 (7): 1398-407, 2005.[PUBMED Abstract]
  36. Goff BA, Mandel LS, Melancon CH, et al.: Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA 291 (22): 2705-12, 2004.[PUBMED Abstract]
  37. Goff BA, Mandel LS, Drescher CW, et al.: Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer 109 (2): 221-7, 2007.[PUBMED Abstract]
  38. Partridge E, Kreimer AR, Greenlee RT, et al.: Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol 113 (4): 775-82, 2009.[PUBMED Abstract]
  39. van Nagell JR, Miller RW, DeSimone CP, et al.: Long-term survival of women with epithelial ovarian cancer detected by ultrasonographic screening. Obstet Gynecol 118 (6): 1212-21, 2011.[PUBMED Abstract]
  40. Burghardt E, Girardi F, Lahousen M, et al.: Patterns of pelvic and paraaortic lymph node involvement in ovarian cancer. Gynecol Oncol 40 (2): 103-6, 1991.[PUBMED Abstract]
  41. Berek JS, Knapp RC, Malkasian GD, et al.: CA 125 serum levels correlated with second-look operations among ovarian cancer patients. Obstet Gynecol 67 (5): 685-9, 1986.[PUBMED Abstract]
  42. Atack DB, Nisker JA, Allen HH, et al.: CA 125 surveillance and second-look laparotomy in ovarian carcinoma. Am J Obstet Gynecol 154 (2): 287-9, 1986.[PUBMED Abstract]
  43. Omura GA, Brady MF, Homesley HD, et al.: Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. J Clin Oncol 9 (7): 1138-50, 1991.[PUBMED Abstract]
  44. van Houwelingen JC, ten Bokkel Huinink WW, van der Burg ME, et al.: Predictability of the survival of patients with advanced ovarian cancer. J Clin Oncol 7 (6): 769-73, 1989.[PUBMED Abstract]
  45. Neijt JP, ten Bokkel Huinink WW, van der Burg ME, et al.: Long-term survival in ovarian cancer. Mature data from The Netherlands Joint Study Group for Ovarian Cancer. Eur J Cancer 27 (11): 1367-72, 1991.[PUBMED Abstract]
  46. Hoskins WJ, Bundy BN, Thigpen JT, et al.: The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage III epithelial ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol 47 (2): 159-66, 1992.[PUBMED Abstract]
  47. Thigpen T, Brady MF, Omura GA, et al.: Age as a prognostic factor in ovarian carcinoma. The Gynecologic Oncology Group experience. Cancer 71 (2 Suppl): 606-14, 1993.[PUBMED Abstract]
  48. Dembo AJ, Davy M, Stenwig AE, et al.: Prognostic factors in patients with stage I epithelial ovarian cancer. Obstet Gynecol 75 (2): 263-73, 1990.[PUBMED Abstract]
  49. Ahmed FY, Wiltshaw E, A'Hern RP, et al.: Natural history and prognosis of untreated stage I epithelial ovarian carcinoma. J Clin Oncol 14 (11): 2968-75, 1996.[PUBMED Abstract]
  50. Monga M, Carmichael JA, Shelley WE, et al.: Surgery without adjuvant chemotherapy for early epithelial ovarian carcinoma after comprehensive surgical staging. Gynecol Oncol 43 (3): 195-7, 1991.[PUBMED Abstract]
  51. Kolomainen DF, A'Hern R, Coxon FY, et al.: Can patients with relapsed, previously untreated, stage I epithelial ovarian cancer be successfully treated with salvage therapy? J Clin Oncol 21 (16): 3113-8, 2003.[PUBMED Abstract]
  52. Schueler JA, Cornelisse CJ, Hermans J, et al.: Prognostic factors in well-differentiated early-stage epithelial ovarian cancer. Cancer 71 (3): 787-95, 1993.[PUBMED Abstract]
  53. Young RC, Walton LA, Ellenberg SS, et al.: Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials. N Engl J Med 322 (15): 1021-7, 1990.[PUBMED Abstract]
  54. Gershenson DM, Silva EG, Mitchell MF, et al.: Transitional cell carcinoma of the ovary: a matched control study of advanced-stage patients treated with cisplatin-based chemotherapy. Am J Obstet Gynecol 168 (4): 1178-85; discussion 1185-7, 1993.[PUBMED Abstract]
  55. Vencken PM, Kriege M, Hoogwerf D, et al.: Chemosensitivity and outcome of BRCA1- and BRCA2-associated ovarian cancer patients after first-line chemotherapy compared with sporadic ovarian cancer patients. Ann Oncol 22 (6): 1346-52, 2011.[PUBMED Abstract]
  56. Safra T, Borgato L, Nicoletto MO, et al.: BRCA mutation status and determinant of outcome in women with recurrent epithelial ovarian cancer treated with pegylated liposomal doxorubicin. Mol Cancer Ther 10 (10): 2000-7, 2011.[PUBMED Abstract]
  57. Rustin GJ, van der Burg ME, Griffin CL, et al.: Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet 376 (9747): 1155-63, 2010.[PUBMED Abstract]
Cellular Classification of Ovarian Epithelial Cancer, FTC, and PPC

Table 1 describes the histologic classification of ovarian epithelial cancer, fallopian tube cancer (FTC), and primary peritoneal cancer (PPC).

Table 1. Ovarian Epithelial Cancer, FTC, and PPC Histologic Classification
Histologic Classification Histologic Subtypes
FTC = fallopian tube cancer; PPC = primary peritoneal cancer.
Serous cystomas Serous benign cystadenomas.
Serous cystadenomas with proliferating activity of the epithelial cells and nuclear abnormalities but with no infiltrative destructive growth (refer to the PDQ summary on Ovarian Low Malignant Potential Tumors Treatment for more information).
Serous cystadenocarcinomas.
Mucinous cystomas Mucinous benign cystadenomas.
Mucinous cystadenomas with proliferating activity of the epithelial cells and nuclear abnormalities but with no infiltrative destructive growth (low malignant potential or borderline malignancy).
Mucinous cystadenocarcinomas.
Endometrioid tumors (similar to adenocarcinomas in the endometrium) Endometrioid benign cysts.
Endometrioid tumors with proliferating activity of the epithelial cells and nuclear abnormalities but with no infiltrative destructive growth (low malignant potential or borderline malignancy).
Endometrioid adenocarcinomas.
Clear cell (mesonephroid) tumors Benign clear cell tumors.
Clear cell tumors with proliferating activity of the epithelial cells and nuclear abnormalities but with no infiltrative destructive growth (low malignant potential or borderline malignancy).
Clear cell cystadenocarcinomas.
Unclassified tumors that cannot be allotted to one of the above groups  
No histology (cytology-only diagnosis)  
Other malignant tumors (malignant tumors other than those of the common epithelial types are not to be included with the categories listed above)  
Stage Information for Ovarian Epithelial Cancer, FTC, and PPC

In the absence of extra-abdominal metastatic disease, definitive staging of ovarian cancer requires surgery. The role of surgery in patients with stage IV ovarian cancer and extra-abdominal disease is yet to be established. If disease appears to be limited to the ovaries or pelvis, it is essential at laparotomy to obtain peritoneal washings and to examine and biopsy or obtain cytologic brushings of the following:

The Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) Staging

The FIGO and the American Joint Committee on Cancer (AJCC) have designated staging to define ovarian epithelial cancer. The FIGO-approved new staging system for ovarian epithelial cancer, fallopian tube cancer (FTC), and primary peritoneal cancer (PPC) is the one most commonly used.[ 2 ][ 3 ]

Table 2. Definitions of FIGO Stage Ia
Stage Definition Illustration
aAdapted from the Fédération Internationale de Gynécologie et d’Obstétrique.[ 2 ]
I Tumor confined to ovaries or fallopian tube(s).  
Three-panel drawing of stage IA, IB, and IC; the first panel (stage IA) shows cancer inside one ovary. The second panel (stage IB) shows cancer inside both ovaries. The third panel (stage IC) shows cancer inside both ovaries, and one ovary has a ruptured capsule. An inset shows cancer cells in the pelvic peritoneum. Also shown are the fallopian tubes, uterus, cervix, and vagina.

画像を拡大する

IA Tumor limited to one ovary (capsule intact) or fallopian tube; no tumor on ovarian or fallopian tube surface; no malignant cells in the ascites or peritoneal washings.  
IB Tumor limited to both ovaries (capsules intact) or fallopian tubes; no tumor on ovarian or fallopian tube surface; no malignant cells in the ascites or peritoneal washings.
IC Tumor limited to one or both ovaries or fallopian tubes, with any of the following:
IC1: Surgical spill intraoperatively.
IC2: Capsule ruptured before surgery or tumor on ovarian or fallopian tube surface.
IC3: Malignant cells present in the ascites or peritoneal washings.
Table 3. Definitions of FIGO Stage IIa
Stage Definition Illustration
aAdapted from the Fédération Internationale de Gynécologie et d’Obstétrique.[ 2 ]
II Tumor involves one or both ovaries or fallopian tubes with pelvic extension (below pelvic brim) or peritoneal cancer (Tp).  
Three-panel drawing of stage IIA, IIB, and stage II primary peritoneal cancer; the first panel (stage IIA) shows cancer inside both ovaries that has spread to the uterus and fallopian tube. The second panel (stage IIB) shows cancer inside both ovaries that has spread to the colon. The third panel (stage II primary peritoneal cancer) shows cancer in the pelvic peritoneum. Also shown are the cervix and vagina.

画像を拡大する

IIA Extension and/or implants on the uterus and/or fallopian tubes and/or ovaries.  
IIB Extension to other pelvic intraperitoneal tissues.
Table 4. Definitions of FIGO Stage IIIa
Stage Definition Illustration
aAdapted from the Fédération Internationale de Gynécologie et d’Obstétrique.[ 2 ]
bIncludes extension of tumor to capsule of liver and spleen without parenchymal involvement of either organ.
III Tumor involves one or both ovaries, or fallopian tubes, or primary peritoneal cancer, with cytologically or histologically confirmed spread to the peritoneum outside of the pelvis and/or metastasis to the retroperitoneal lymph nodes.  
IIIA Metastasis to the retroperitoneal lymph nodes with or without microscopic peritoneal involvement beyond the pelvis.  
Drawing of stage IIIA shows cancer inside both ovaries that has spread to (a) lymph nodes behind the peritoneum. Also shown is (b) microscopic cancer cells that have spread to the omentum. The small intestine, colon, fallopian tubes, uterus, and bladder are also shown.

画像を拡大する

IIIA(i) Positive retroperitoneal lymph nodes only (cytologically or histologically proven).  
IIIA(ii) Metastasis >10 mm in greatest dimension.
IIIA2 Microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes.
IIIB Macroscopic peritoneal metastases beyond the pelvic brim ≤2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes.  
Drawing of stage IIIB shows cancer inside both ovaries that has spread to the omentum. The cancer in the omentum is 2 centimeters or smaller. An inset shows 2 centimeters is about the size of a peanut. Also shown are the small intestine, colon, fallopian tubes, uterus, bladder, and lymph nodes behind the peritoneum.

画像を拡大する

IIIC Macroscopic peritoneal metastases beyond the pelvic brim >2 cm in greatest dimension, with or without metastases to the retroperitoneal nodes.b  
Drawing of stage IIIC shows cancer inside both ovaries that has spread to the omentum. The cancer in the omentum is larger than 2 centimeters. An inset shows 2 centimeters is about the size of a peanut. Also shown are the small intestine, colon, fallopian tubes, uterus, bladder, and lymph nodes behind the peritoneum.

画像を拡大する

Table 5. Definitions of FIGO Stage IVa
Stage Definition Illustration
aAdapted from the Fédération Internationale de Gynécologie et d’Obstétrique.[ 2 ]
bParenchymal metastases are stage IVB.
IV Distant metastasis excluding peritoneal metastases.  
Drawing of stage IV shows other parts of the body where ovarian cancer, fallopian tube cancer, and primary peritoneal cancer may spread, including the lung, liver, bone, and lymph nodes in the groin. An inset on the top shows extra fluid around the lung. An inset on the bottom shows cancer cells spreading through the blood and lymph system to another part of the body where metastatic cancer has formed.

画像を拡大する

IVA Pleural effusion with positive cytology.  
IVB Metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside of the abdominal cavity).b
参考文献
  1. Hoskins WJ: Surgical staging and cytoreductive surgery of epithelial ovarian cancer. Cancer 71 (4 Suppl): 1534-40, 1993.[PUBMED Abstract]
  2. Mutch DG, Prat J: 2014 FIGO staging for ovarian, fallopian tube and peritoneal cancer. Gynecol Oncol 133 (3): 401-4, 2014.[PUBMED Abstract]
  3. Ovary, fallopian tube, and primary peritoneal carcinoma. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 681-90.[PUBMED Abstract]
Treatment Option Overview

Treatment options for patients with all stages of ovarian epithelial cancer, fallopian tube cancer (FTC), and primary peritoneal cancer (PPC) have consisted of surgery followed by platinum-based chemotherapy.

Early stage refers to stages I and II. However, because of high recurrence rates for stage II patients in early-stage disease trials, patients with stage II cancers have been included with patients who have more advanced-stage cancer in Gynecologic Oncology Group clinical trials since 2009. Going forward, stage I will remain a separate category for treatment considerations, but high-grade serous stage II cancers are likely to be included with more advanced stages.

Numerous clinical trials are in progress to refine existing therapies and test the value of different approaches to postoperative drug and radiation therapy. Patients with any stage of ovarian cancer are appropriate candidates for clinical trials.[ 1 ][ 2 ] Information about ongoing clinical trials is available from the NCI website.

The treatment options for ovarian epithelial cancer, FTC, and PPC are presented in Table 6.

Table 6. Treatment Options for Ovarian Epithelial Cancer, FTC, and PPC
Stage Treatment Options
OS = overall survival; PARP = poly (ADP) ribose-polymerase.
Early stage Surgery with or without chemotherapy
Advanced stage Surgery followed by systemic chemotherapy
Surgery followed by intraperitoneal (IP) chemotherapy
Surgery followed by chemotherapy and bevacizumab
Surgery followed by chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors
Chemotherapy followed by surgery (possibly followed by IP therapy).
Chemotherapy for patients who cannot have surgery (although the impact on OS has not been proven)
Recurrent Platinum-containing chemotherapy regimens
Bevacizumab, other targeted drugs, and PARP inhibitors with or without chemotherapy
Chemotherapy
Chemotherapy and/or bevacizumab
参考文献
  1. Ozols RF, Young RC: Ovarian cancer. Curr Probl Cancer 11 (2): 57-122, 1987 Mar-Apr.[PUBMED Abstract]
  2. Cannistra SA: Cancer of the ovary. N Engl J Med 329 (21): 1550-9, 1993.[PUBMED Abstract]
Early-Stage Ovarian Epithelial Cancer, FTC, and PPC Treatment

Early stage refers to stage I and stage II. However, because of high recurrence rates for stage II patients in early-stage disease trials, patients with stage II cancers have been included with patients who have more advanced-stage cancer in Gynecologic Oncology Group (GOG) clinical trials since 2009. Going forward, stage I will remain a separate category for treatment considerations, but high-grade serous stage II cancers are likely to be included with more advanced stages.

Standard Treatment Options for Early-Stage Ovarian Epithelial Cancer, FTC, and PPC

Standard treatment options for early-stage ovarian epithelial, fallopian tube cancer (FTC), and primary peritoneal cancer (PPC) include the following:

  1. Surgery with or without chemotherapy.

Surgery with or without chemotherapy

If the tumor is well differentiated or moderately well differentiated, surgery alone may be adequate treatment for patients with stage IA or IB disease. Surgery includes hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The undersurface of the diaphragm is visualized and biopsied. Biopsies of the pelvic and abdominal peritoneum and the pelvic and para-aortic lymph nodes are also performed. Peritoneal washings are routinely obtained.[ 1 ][ 2 ] In patients who desire childbearing and have grade I tumors, unilateral salpingo-oophorectomy may be associated with a low risk of recurrence.[ 3 ]

In the United States, except for the most favorable subset of patients (those with stage IA well-differentiated disease), evidence based on double-blinded, randomized, controlled trials with total mortality endpoints supports adjuvant treatment with cisplatin, carboplatin, and paclitaxel.

Evidence (surgery with or without chemotherapy):

  1. In two large European trials, the European Organization for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm trial (EORTC-ACTION) and International Collaborative Ovarian Neoplasm trial (MRC-ICON1 [NCT00002477]), patients with stage IA (grade II) and stage IB (grade III), all stage IC and stage II ovarian epithelial, and all stage I and stage IIA clear cell carcinoma were randomly assigned to receive adjuvant chemotherapy or observation.[ 4 ][ 5 ][ 6 ]
    1. The EORTC-ACTION trial required at least four cycles of carboplatin or cisplatin-based chemotherapy as treatment. Although surgical staging criteria were monitored, inadequate staging was not an exclusion criterion.[ 4 ]
    2. The MRC-ICON1 trial randomly assigned patients to six cycles of single-agent carboplatin or cisplatin or platinum-based chemotherapy (usually cyclophosphamide, doxorubicin, and cisplatin) versus observation and had entry criteria similar to the EORTC-ACTION trial; however, the MRC-ICON1 trial did not monitor whether adequate surgical staging was performed.[ 5 ] When the results of the trials were combined, the difference in OS achieved statistical significance.
    3. An analysis of pooled data from both studies demonstrated the following:[ 6 ][Level of evidence: 1iA]
  2. The GOG-0157 trial evaluated whether six cycles of chemotherapy were superior to three cycles for patients with early-stage, high-risk epithelial ovarian cancer after primary surgery. Eligible patients were those with stage IA grade 3 or clear cell histology, stage IB grade 3 or clear cell histology, all stage IC, and all stage II. Patients were randomly assigned to receive either three or six cycles of the combination of paclitaxel (175 mg/m2 administered over 3 hours) and carboplatin dosed (area under the curve, 7.5) over 30 minutes and given every 21 days. The primary endpoint was RFS, and the study was powered to detect a 50% decrease in the recurrence rate at 5 years. A total of 427 patients were eligible.[ 8 ][Level of evidence: 1iiDi]

    Given the increased risk of recurrence in patients with stage II disease and combined with an earlier trial, the Ovarian Committee of the GOG has opted to include patients with stage II disease in advanced ovarian cancer trials. The interpretation of this study, including findings on subset analyses, has been a source of controversy.

  3. Patients with stage II ovarian cancer were enrolled in a Japanese Gynecology Oncology Group study (JGOG-3016 [NCT00226915]) that tested a weekly dosing schedule versus the conventional every-3-week dosing schedule in first-line ovarian cancer.[ 9 ][ 10 ][ 11 ]

Clinical trials evaluating the following treatment approaches have been performed:

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献
  1. Young RC, Decker DG, Wharton JT, et al.: Staging laparotomy in early ovarian cancer. JAMA 250 (22): 3072-6, 1983.[PUBMED Abstract]
  2. Fader AN, Java J, Ueda S, et al.: Survival in women with grade 1 serous ovarian carcinoma. Obstet Gynecol 122 (2 Pt 1): 225-32, 2013.[PUBMED Abstract]
  3. Zanetta G, Chiari S, Rota S, et al.: Conservative surgery for stage I ovarian carcinoma in women of childbearing age. Br J Obstet Gynaecol 104 (9): 1030-5, 1997.[PUBMED Abstract]
  4. Trimbos JB, Vergote I, Bolis G, et al.: Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma: European Organisation for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm trial. J Natl Cancer Inst 95 (2): 113-25, 2003.[PUBMED Abstract]
  5. Colombo N, Guthrie D, Chiari S, et al.: International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst 95 (2): 125-32, 2003.[PUBMED Abstract]
  6. Trimbos JB, Parmar M, Vergote I, et al.: International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst 95 (2): 105-12, 2003.[PUBMED Abstract]
  7. Young RC: Early-stage ovarian cancer: to treat or not to treat. J Natl Cancer Inst 95 (2): 94-5, 2003.[PUBMED Abstract]
  8. Bell J, Brady MF, Young RC, et al.: Randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 102 (3): 432-9, 2006.[PUBMED Abstract]
  9. Katsumata N, Yasuda M, Takahashi F, et al.: Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet 374 (9698): 1331-8, 2009.[PUBMED Abstract]
  10. Katsumata N, Yasuda M, Isonishi S, et al.: Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. Lancet Oncol 14 (10): 1020-6, 2013.[PUBMED Abstract]
  11. Scambia G, Salutari V, Amadio G: Controversy in treatment of advanced ovarian cancer. Lancet Oncol 14 (10): 920-1, 2013.[PUBMED Abstract]
  12. Vergote IB, Vergote-De Vos LN, Abeler VM, et al.: Randomized trial comparing cisplatin with radioactive phosphorus or whole-abdomen irradiation as adjuvant treatment of ovarian cancer. Cancer 69 (3): 741-9, 1992.[PUBMED Abstract]
  13. Piver MS, Lele SB, Bakshi S, et al.: Five and ten year estimated survival and disease-free rates after intraperitoneal chromic phosphate; stage I ovarian adenocarcinoma. Am J Clin Oncol 11 (5): 515-9, 1988.[PUBMED Abstract]
  14. Bolis G, Colombo N, Pecorelli S, et al.: Adjuvant treatment for early epithelial ovarian cancer: results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P). G.I.C.O.G.: Gruppo Interregionale Collaborativo in Ginecologia Oncologica. Ann Oncol 6 (9): 887-93, 1995.[PUBMED Abstract]
  15. Piver MS, Malfetano J, Baker TR, et al.: Five-year survival for stage IC or stage I grade 3 epithelial ovarian cancer treated with cisplatin-based chemotherapy. Gynecol Oncol 46 (3): 357-60, 1992.[PUBMED Abstract]
  16. McGuire WP: Early ovarian cancer: treat now, later or never? Ann Oncol 6 (9): 865-6, 1995.[PUBMED Abstract]
Advanced-Stage Ovarian Epithelial Cancer, FTC, and PPC Treatment

Treatment options for patients with all stages of ovarian epithelial cancer, fallopian tube cancer (FTC), and primary peritoneal cancer (PPC) have consisted of surgery followed by platinum-based chemotherapy. Because of high recurrence rates for stage II patients in early-stage disease trials, patients with stage II cancers have been included with patients who have more advanced-stage cancer in Gynecologic Oncology Group (GOG) clinical trials since 2009. Going forward, stage I will remain a separate category for treatment considerations, but high-grade serous stage II cancers are likely to be included with more advanced stages.

Standard Treatment Options for Advanced-Stage Ovarian Epithelial Cancer, FTC, and PPC

Standard treatment options for advanced-stage ovarian epithelial cancer, FTC, and PPC include the following:

  1. Surgery followed by systemic chemotherapy.
  2. Surgery followed by intraperitoneal (IP) chemotherapy.
  3. Surgery followed by chemotherapy and bevacizumab.
  4. Surgery followed by chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors
  5. Chemotherapy followed by surgery (possibly followed by IP therapy).
  6. Chemotherapy for patients who cannot have surgery (although the impact on overall survival [OS] has not been proven).

After initial therapy, consolidation and/or maintenance therapy have not been shown to improve survival. (Refer to the Consolidation and/or maintenance therapy section of this summary for more information.)

Patients diagnosed with advanced disease are treated with surgery and chemotherapy; however, the outcome is generally less favorable for patients with stage IV disease. The role of surgery for patients with stage IV disease is unclear, but in most instances, the bulk of the disease is intra-abdominal, and surgical procedures similar to those used in the management of patients with stage III disease are applied. The options for IP regimens are also less likely to apply both practically (as far as inserting an IP catheter at the outset) and theoretically (aimed at destroying microscopic disease in the peritoneal cavity) in patients with stage IV disease.

Surgery is used to adequately stage the disease and as a therapeutic modality. Surgery includes total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy and debulking of as much gross tumor as can safely be performed.

While primary cytoreductive surgery may not correct for biologic characteristics of the tumor, considerable evidence indicates that the volume of disease left at the completion of the primary surgical procedure is related to patient survival.[ 1 ][ 2 ][ 3 ][ 4 ] A literature review showed that patients with optimal cytoreduction had a median survival of 39 months compared with survival of only 17 months in patients with suboptimal residual disease.[ 1 ][Level of evidence: 3iA]

Results of a retrospective analysis of 349 patients with postoperative residual masses no larger than 1 cm suggested that patients who present at the outset with large-volume disease and achieve small-volume disease by surgical debulking have poorer outcomes than similar patients who present with small-volume disease.[ 2 ] Gradual improvement in survival with decreasing residual tumor volume is likely. Although the association may not be causal, retrospective analyses, including a meta-analysis of patients receiving platinum-based chemotherapy, have also found cytoreduction to be an independent prognostic variable for survival.[ 3 ][ 4 ] An analysis of 2,655 patients enrolled in GOG-0182 (NCT00011986) found that only cytoreduction to node-visible disease that is R0 (i.e., complete surgical resection) had an independent effect on survival.[ 5 ]

For the past three decades, the GOG has conducted separate trials for women whose disease has been optimally cytoreduced (defined as ≤1 cm residuum) and for those who had suboptimal cytoreductions (>1 cm residuum). The extent of residual disease after the initial surgery is a determinant of outcome in most series [ 1 ][ 2 ][ 3 ][ 4 ] and has been used in the design of clinical trials, particularly by the GOG.

On the basis of these findings, different standard treatment approaches may be used for patients with optimally cytoreduced stage III disease versus patients with suboptimally cytoreduced stage III and stage IV disease. Most studies evaluating IP treatments require making allocations on the basis of the extent of cytoreduction. (Refer to the Surgery followed by IP chemotherapy section of this summary for more information.)

Long-term follow-up of suboptimally debulked stage III and stage IV patients showed a 5-year survival rate lower than 10% with platinum-based combination therapy before the current generation of trials, including taxanes.[ 6 ] By contrast, optimally debulked stage III patients treated with a combination of intravenous (IV) taxane and IP platinum plus taxane achieved a median survival of 66 months in a GOG trial.[ 7 ][Level of evidence: 1iiA]

Surgery followed by systemic chemotherapy

For patients with residual disease larger than 1 cm after surgery, systemic chemotherapy is the standard. Platinum agents, such as cisplatin or its second-generation analog, carboplatin, given either alone or in combination with other drugs, are the foundation of chemotherapy regimens used. Trials by various cooperative groups (1999–2010) addressed issues of optimal dose-intensity [ 8 ][ 9 ][ 10 ] for both cisplatin and carboplatin,[ 11 ] schedule,[ 12 ] and the equivalent results obtained with either of these platinum drugs, usually in combination with cyclophosphamide.[ 13 ]

With the introduction of the taxane paclitaxel, two trials confirmed the superiority of cisplatin combined with paclitaxel when compared with the previous standard treatment of cisplatin plus cyclophosphamide.[ 14 ][ 15 ] However, two trials that compared single-agent paclitaxel with either cisplatin or carboplatin (ICON2 and GOG-132) failed to confirm such superiority in all outcome parameters (i.e., response, time-to-progression, and survival) (see Table 7 for a list of these studies).

Based on the evidence, the initial standard treatment for patients with ovarian cancer is the combination of cisplatin or carboplatin with paclitaxel (defined as induction chemotherapy).

Evidence (combination of cisplatin or carboplatin with paclitaxel)

  1. GOG-132 was widely regarded as showing that sequential treatment with cisplatin and paclitaxel was equivalent to the combination of cisplatin- or carboplatin-plus-paclitaxel; however, many patients crossed over before disease progression. Moreover, the cisplatin-only arm was more toxic because it utilized a 100 mg/m2 dose.[ 16 ]
  2. The Medical Research Council study (MRC-ICON3), while having fewer early crossovers, could be interpreted similarly in regard to the impact of sequential treatment on survival.[ 17 ]

Since the adoption of the standard combination of platinum plus taxane nearly worldwide, clinical trials have demonstrated the following:

  1. Noninferiority of carboplatin plus paclitaxel versus cisplatin plus paclitaxel.[ 14 ][ 15 ][ 18 ]
  2. Noninferiority of carboplatin plus paclitaxel versus carboplatin plus docetaxel.[ 19 ]
  3. No advantage but increased toxic effects of adding epirubicin to the carboplatin plus paclitaxel doublet.[ 20 ]
  4. Noninferiority of carboplatin plus paclitaxel versus sequential carboplatin-containing doublets with either gemcitabine or topotecan; or, triplets with the addition of gemcitabine or pegylated liposomal doxorubicin to the reference doublet as shown below:[ 21 ][ 22 ]
    1. From February 2001 to September 2004, 4,312 women with stage III or stage IV ovarian epithelial cancer, FTC, or PPC participating in the GOG-0182 trial were randomly assigned to four different experimental arms or to a reference treatment consisting of carboplatin (area under the curve [AUC], 6) and paclitaxel (175 mg/m2) every 3 weeks for eight cycles.[ 21 ] Stratification factors were residual-disease status and the intention to perform interval debulking surgery.

      In this large study consisting of two arms of patients with Fédération Internationale de Gynécologie et d’Obstétrique stage III disease (84% in one arm and 87% in the other arm), the extent of cytoreduction was an important prognostic factor in OS, as expected.

In gynecologic cancer, as opposed to breast cancer, weekly paclitaxel was not explored in phase III trials before 2004. The positive results from the Japanese Gynecologic Oncology Group (JGOG) 3016 study have been widely adopted and also led to new divided-dose paclitaxel studies.

Evidence (dose-dense [weekly] treatment schedule):

  1. A JGOG trial accrued 637 patients (JGOG-3016 [NCT00226915]) and randomly assigned them to six to nine cycles of weekly (dose-dense) paclitaxel (80 mg/m2) or to the standard every-21-day schedule of paclitaxel at 180 mg/m2. Both regimens were given with carboplatin (AUC, 6) in every-3-week cycles. With a primary endpoint of PFS, an increase from 16 to 21 months in the PFS of the weekly paclitaxel-based regimen was sought.[ 23 ][ 24 ] Although more toxic, the weekly paclitaxel regimen did not adversely affect quality of life when compared with the intermittent schedule.[ 25 ][Level of evidence: 1iiDiii]

    Other than ethnicity, this trial population differed from other studies in the following ways:

    Study results demonstrated the following:

  2. In a phase III trial (MITO-7 [NCT00660842]), the outcomes of 406 patients assigned to weekly paclitaxel (60 mg/m2) administered with weekly carboplatin (AUC, 2) were compared with those of 404 patients receiving the conventional every-3-week regimen of paclitaxel and carboplatin.[ 26 ][Level of evidence: 1iiA]
  3. GOG-0262 [NCT01167712] is a phase III study that compared weekly paclitaxel (80 mg/m2) to every-3-week dosing (175 mg/m2), both with the conventional every-3-week carboplatin (AUC, 6) regimen.[ 27 ][Level of evidence: 1iiDiii] An option to give bevacizumab every 3 weeks beginning with cycle two and continuing until cycle six and followed by bevacizumab alone for 1 year, as in GOG-0218, was included for both arms. This option was applied in about 84% of all patients.
Table 7. Selected Phase III Studies of Intravenous Adjuvant Therapy for Advanced Ovarian Cancer After Initial Surgery
Trial Treatment Regimens No. of Patients Progression-free Survival (mo) Overall Survival (mo)
AUC = area under the curve; EORTC = European Organization for Research and Treatment of Cancer; Est = estimated; GOG = Gynecologic Oncology Group; ICON = International Collaboration on Ovarian Neoplasms; JGOG = Japanese Gynecologic Oncology Group; MITO = Multicentre Italian Trials in Ovarian cancer; MRC = Medical Research Council; No. = number; NR = not reported.
aControl arms are bolded.
bStatistically inferior result (P < .001–< .05).
cOptimally debulked only.
dEvery 3 weeks for six cycles unless specified.
eJGOG-3016 included stage II patients.
GOG-111 (1990–1992)a [ 28 ] Paclitaxel (135 mg/m2, 24 h) and cisplatin (75 mg/m2) 184 18 38
Cyclophosphamide (750 mg/m2) and cisplatin (75 mg/m2) 202 13b 24b
EORTC-55931 Paclitaxel (175 mg/m2, 3 h) and cisplatin (75 mg/m2) 162 15.5 35.6
Cyclophosphamide (750 mg/m2) and cisplatin (75 mg/m2) 161 11.5b 25.8b
GOG-132 (1992–1994) Paclitaxel (135 mg/m2, 24 h) and cisplatin (75 mg/m2) 201 14.2 26.6
Cisplatin (100 mg/m2) 200 16.4 30.2
Paclitaxel (200 mg/m2, 24 h) 213 11.2b 26
MRC-ICON3 [ 17 ] Paclitaxel (175 mg/m2, 3 h) and carboplatin (AUC, 6) 478 17.3 36.1
Carboplatin (AUC, 6) 943 16.1 35.4
Paclitaxel (175 mg/m2, 3 h) and carboplatin (AUC, 6) 232 17 40
Cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) and cisplatin (50 mg/m2) 421 17 40
GOG-158 (1995–1998)c Paclitaxel (135 mg/m2, 24 h) and cisplatin (75 mg/m2)d 425 14.5 48
Paclitaxel (175 mg/m2, 3 h) and carboplatin (AUC, 6) 415 15.5 52
JGOG-3016 (2002–2004)e Paclitaxel (180 mg/m2) and carboplatin (AUC, 6)d 319 17.5 62.2
Paclitaxel (80 mg/m2) and carboplatin (AUC, 6) 312 28.5 100.5
MITO-7 [ 26 ][ 29 ] Paclitaxel (175 mg/m2) and carboplatin (AUC, 6)d 404 17.3 NR
Paclitaxel (60 mg/m2) and carboplatin (AUC, 6) 406 18.3 NR
GOG-0262 [ 27 ] Paclitaxel (80 mg/m2) and carboplatin (AUC, 6) plus optional bevacizumab cycles 2–6, and every 3 wk until progression 346 14.7 Est 42
Paclitaxel (175 mg/m2) and carboplatin (AUC, 6) (× 6 cycles) plus optional bevacizumab cycles 2–6, and every 3 wk until progression 346 14.0 Est 42
GOG-218 Paclitaxel (175 mg/m2) and carboplatin (AUC, 6) (× 6 cycles) and placebo cycles 2–22 625 10.3 39.3
Paclitaxel (175 mg/m2) and carboplatin (AUC, 6) (× 6 cycles) and bevacizumab cycles 2–6, and placebo cycles 7–22 625 11.2 38.7
Paclitaxel (175 mg/m2) and carboplatin (AUC, 6) (× 6 cycles) and bevacizumab cycles 2–22 623 14.1 39.7
ICON7 [ 30 ] Paclitaxel (175 mg/m2) and carboplatin (AUC, 5 or 6) and bevacizumab 7.5 mg/kg × 6 cycles and bevacizumab alone cycles 7–18 764 19.0 45.5
Paclitaxel (175 mg/m2) and carboplatin (AUC, 5 or 6) × 6 cycles 764 17.3 44.6

Surgery followed by IP chemotherapy

The pharmacologic basis for the delivery of anticancer drugs by the IP route was established in the late 1970s and early 1980s. When several drugs were studied, mostly in the setting of minimal residual disease at reassessment after patients had received their initial chemotherapy, cisplatin alone and in combination received the most attention. Favorable outcomes from IP cisplatin were most often seen when tumors had shown responsiveness to platinum therapy and with small-volume tumors (usually defined as tumors <1 cm).[ 31 ]

In the 1990s, randomized trials were conducted to evaluate whether the IP route would prove superior to the IV route. IP cisplatin was the common denominator of these randomized trials.

Hyperthermic peritoneal chemotherapy (HIPEC) is another pharmacologically based modality to enhance the antitumor effects via direct drug delivery to peritoneal surfaces. It was initially tested against mucinous tumors of gastrointestinal origin.[ 32 ] Increasingly, HIPEC is being applied to ovarian cancers, with considerable variation in patient selection, drugs administered, and time at target temperatures (most often 30 minutes at 42°C). While exploratory trials are ongoing in the setting of recurrent ovarian cancer, such modalities should not be used as a substitute for IP cisplatin-based regimens after initial therapy.[ 33 ] The role of HIPEC remains experimental in the treatment of patients with high-grade serous ovarian cancers.

Evidence (surgery followed by IP chemotherapy):

  1. The use of IP cisplatin as part of the initial approach in patients with stage III optimally debulked ovarian cancer is supported principally by the results of three randomized clinical trials (SWOG-8501, GOG-0114, and GOG-0172 [NCT00003322]).[ 7 ][ 34 ][ 35 ] These studies tested the role of IP drugs (IP cisplatin in all three studies and IP paclitaxel in the last study) against the standard IV regimen.

    Specifically, the most recent study, GOG-0172, demonstrated the following:[ 7 ][Level of evidence:1iiA]

    An updated combined analysis of GOG-0114 and GOG-0172 included 876 patients with a median follow-up of 10.7 years and reported the following results.[ 36 ]

    Accordingly, efforts are under way by the GOG to examine some modifications of the IP regimen used in GOG-0172 to improve its tolerability (e.g., to reduce by ≥25% the total 3-hour amount of cisplatin given; and, to shift from the less practical 24-hour IV administration of paclitaxel to a 3-hour IV administration.)

  2. A Cochrane-sponsored meta-analysis of all randomized IP-versus-IV trials showed an HR of 0.79 for disease-free survival and 0.79 for OS, favoring the IP arms.[ 37 ]
  3. In another meta-analysis of seven randomized trials assessing IP versus systemic chemotherapy conducted by Cancer Care of Ontario, the relative ratio (RR) of disease progression at 5 years based on the three trials that reported this endpoint was 0.91 (95% CI, 0.85–0.98), and the RR of death at 5 years based on six trials was 0.88 (95% CI, 0.81–0.95) for the IP route.[ 38 ]

Surgery followed by chemotherapy and bevacizumab

Two phase III trials (GOG-0218 [NCT00262847] and ICON7 [NCT00483782]) have evaluated the role of bevacizumab in first-line therapy for ovarian epithelial cancer, FTC, and PPC after surgical cytoreduction.[ 39 ][ 40 ] Both trials showed a modest improvement in PFS when bevacizumab was added to initial chemotherapy and continued every 3 weeks for 16 and 12 additional cycles, as a maintenance phase.

Evidence (surgery followed by chemotherapy and bevacizumab):

  1. GOG-0218 was a double-blinded, randomized, controlled trial that included 1,873 women with stage III or IV disease, all of whom received chemotherapy—carboplatin (AUC, 6) and paclitaxel (175 mg/m2 for six cycles). Forty percent of the women had suboptimally resected stage III disease, and 26% had stage IV disease. The primary endpoint of the study was PFS.[ 39 ][Level of evidence:1iDiii] Participants were randomly assigned to receive the following:

    Results from the trial demonstrated the following:

  2. ICON7 randomly assigned 1,528 women after initial surgery to chemotherapy—carboplatin (AUC, 5 or 6) plus paclitaxel (175 mg/m2 for six cycles)—or to chemotherapy plus bevacizumab (7.5 mg/kg for six cycles), followed by bevacizumab alone for an additional 12 cycles. Nine percent of patients had early-stage, high-grade tumors; 70% had stage IIIC or IV disease; and 26% had more than 1 cm of residual tumor before initiating chemotherapy. PFS was the main outcome measure.[ 40 ][Level of evidence: 1iiDiii]
    1. Median PFS was 17.3 months in the control group and 19 months in the bevacizumab group. HR disease progression or death in the bevacizumab group was 0.81 (95% CI, 0.70–0.94; P = .004).
    2. Grade 3 or higher adverse events were more common in the bevacizumab group, with an increase in bleeding, hypertension (grade 2 or higher), thromboembolic events (grade 3 or higher), and gastrointestinal perforations.
    3. Quality of life was not different between the two groups.
    4. In 2015, the ICON7 authors reported an updated survival analysis.[ 30 ]

In summary, the evidence does not support the use of bevacizumab as front-line therapy because the gain in PFS comes with increased toxicity, without improvement in OS or quality of life.

Surgery followed by chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors

PARP is a family of enzymes involved in base-excision repair of DNA single-strand breaks. In patients with homologous recombination deficiency, including patients with germline BRCA1 or BRCA2 (gBRCA) mutations or with nongermline homologous recombination deficiency–positive tumors, the inhibition of PARP results in the production of double-strand breaks of DNA. Human DNA repair mechanisms largely rely on one intact copy of the gene. Cells with a double-strand break are usually targeted for cell death. This susceptibility of BRCA-deficient or BRCA-mutant cells to PARP inhibition,[ 41 ][ 42 ] has spurred the clinical development of this class of agents. Initially, these agents were tested in women who had been pretreated with chemotherapy. (Refer to the Bevacizumab, other targeted drugs, and poly(ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section of this summary for more information.)

Evidence (surgery followed by chemotherapy and PARP inhibitors):

  1. A double-blind phase III trial (SOLO-1) (NCT01844986) compared maintenance olaparib (300 mg tablets bid) with a placebo in patients with newly diagnosed, high-grade serous or endometrioid advanced ovarian cancer with mutations of BRCA1, BRCA2, or both, who had a complete or partial clinical response after platinum-based chemotherapy.[ 43 ] The study of 391 randomly assigned patients ran from September 2013 to March 2015. Of those patients, 260 were assigned to receive olaparib, and 131 patients were assigned to receive a placebo. All but three patients had germline mutations in BRCA1 (n = 191) or BRCA2 (n = 66). The analysis of the primary endpoint was stopped after 2 years if there was no evidence of disease or was continued until investigator-assessed disease progression. Patients with partial responses at 2 years were permitted to receive the intervention in a blinded manner. Crossover was not specified, but after discontinuation, patients could receive treatments at the discretion of the investigator. The primary endpoint was PFS, which was defined as from the time of randomization to objective disease progression on imaging (q 12 weeks up to 3 years), or death from any cause.

    The trial results support the use of maintenance olaparib as consolidation in this preselected population. This is the first indication of a PARP inhibitor following first-line chemotherapy and achieving complete or partial responses in the presence of germline BRCA1 and BRCA2 mutations.

Chemotherapy followed by surgery

Two phase III studies compared the outcome of standard primary cytoreductive surgery with that of neoadjuvant chemotherapy followed by interval cytoreductive surgery; both studies (described below) demonstrated that PFS and OS were noninferior with the use of primary cytoreductive surgery.[ 44 ][ 45 ]

Evidence (chemotherapy followed by surgery):

  1. Between 1998 and 2006, a study led by the European Organization for the Research and Treatment of Cancer (EORTC) Gynecological Cancer Group, together with the National Cancer Institute of Canada Clinical Trials Group (EORTC-55971 [NCT00003636]), included 670 women with stages IIIC and IV ovarian epithelial cancer, FTC, and PPC.[ 44 ][Level of evidence: 1iiA] The women were randomly assigned to undergo primary debulking surgery followed by at least six courses of platinum-based chemotherapy or to receive three courses of neoadjuvant platinum-based chemotherapy followed by interval debulking surgery, and at least three more courses of platinum-based chemotherapy.

    Methods included efforts to ensure accuracy of diagnosis (e.g., rule out peritoneal carcinomatosis of gastrointestinal origin) and stratification by largest preoperative tumor size (excluding ovaries) (<5 cm, >5 cm–10 cm, >10 cm–20 cm, or >20 cm). Other stratification factors included institution, method of biopsy (i.e., image-guided, laparoscopy, laparotomy, or fine-needle aspiration), and tumor stage (i.e., stage IIIC or IV). The primary endpoint of the study was OS, with primary debulking surgery considered the standard.[ 44 ][Level of evidence: 1iiA]

  2. Between 2004 and 2010, a group of 87 hospitals in the United Kingdom and New Zealand enrolled 550 women with stage III or IV ovarian epithelial cancer and randomly assigned them to undergo primary cytoreductive surgery followed by six cycles of chemotherapy or primary (neoadjuvant) chemotherapy for three cycles, followed by surgery and three additional cycles of chemotherapy. In contrast to the EORTC study, the chemotherapy consisted of conventional carboplatin (AUC, 5 or AUC, 6) and paclitaxel (175 mg/m2, in 76% of patients), or carboplatin alone (23% of patients), or nonpaclitaxel chemotherapy (1% of patients).[ 45 ][Level of evidence: 1iiA]

    A minimization method was used to randomly assign patients in a 1:1 ratio. Participants were stratified by randomizing center, largest radiologic tumor, and prespecified chemotherapy regimen. The primary endpoint was to establish noninferiority, with the upper bound of a one-sided 90% CI for the HRdeath at less than 1.18.

These studies and additional observational and partially published phase III studies have led to the publication of a Clinical Practice Guideline on behalf of the Society of Gynecologic Oncology and the American Society of Clinical Oncology.[ 46 ]

HIPEC has been used for peritoneal carcinomatosis from various origins (such as appendiceal and colorectal cancers and peritoneal mesotheliomas), mostly for chemotherapy-resistant disease and after extensive cytoreductive debulking surgery. Experience with HIPEC spans more than two decades after initial publications that have since been summarized.[ 47 ]

Evidence (HIPEC after chemotherapy and surgery):

  1. The final results of a phase III, open-label Dutch study NCT00426257) have been published. The study was performed in eight hospitals and included 245 patients with newly diagnosed ovarian cancer who were at least stable after receiving three cycles of carboplatin (AUC 5–6) and paclitaxel 175 mg/m2, both of which were given by IV every 3 weeks.[ 48 ] Randomization took place at the time of surgery, and patients were assigned to undergo either cytoreductive surgery without HIPEC (n = 123) or with HIPEC (n = 122). All patients subsequently received three additional cycles of IV chemotherapy. The study was reported with a median follow-up of 4.7 years, after the surgical intervention. HIPEC consisted of perfusion of the abdominal cavity with cisplatin 100 mg/m2 in heated saline at 40°C (104°F) that was maintained for 60 minutes. Sodium thiosulfate was given at the start of the perfusion as an IV bolus of 9 g/m2 in 200 mL followed by continuous infusion IV (12 g/m2 in 1L) for 6 hours.[ 49 ]

In the institutions that have experience performing HIPEC, adverse events were comparable in the two groups. Patients in the HIPEC group had higher incidences of ileus (3% vs. 8%), fever (8% vs. 12%), and thromboembolic events (2% vs. 6%), but in that group, there were smaller differences in electrolyte changes (5% vs. 6%) and neuropathy (27% vs. 31%) than did patients in the surgery group, and both groups of patients had added IV chemotherapy. The use of sodium thiosulfate most likely accounts for this favorable safety profile vis-à-vis cisplatin, which was given as part of HIPEC in a published phase I trial.[ 50 ] HIPEC should be considered an option for patients who receive neoadjuvant therapy if they have access to a surgical team who has experience performing HIPEC.

Consolidation and/or maintenance therapy

Phase III trials of consolidation and/or maintenance therapy have been carried out with cytotoxic drugs that contribute to the treatment of recurrent ovarian cancer, vaccines, and radioimmunoconjugates listed below with mostly negative results, and with some biologicals (such as bevacizumab, discussed in a separate section above). These treatments have included the following:

Trials ongoing with anti-angiogenic drugs (other than bevacizumab) and poly (ADP-ribose) polymerase (PARP) inhibitors are described in the Treatment Options under Clinical Evaluation section that follows.

Treatment Options Under Clinical Evaluation

Trials are ongoing with anti-angiogenic drugs (other than bevacizumab) and with PARP inhibitors. PARP is a family of enzymes involved in base-excision repair of DNA single-strand breaks. In patients with homologous recombination deficiency, including patients with germline BRCA1 or BRCA2 (gBRCA) mutations or with nongermline homologous recombination deficiency–positive tumors, inhibition of PARP results in production of double-strand breaks of DNA. Human DNA repair mechanisms largely rely on one intact copy of the gene; cells with a double-strand break are usually targeted for cell death. This susceptibility of BRCA-deficient or BRCA-mutant cells to PARP inhibition [ 41 ][ 42 ] has spurred the clinical development of this class of agents. Sensitivity to platinum compounds is a feature of homologous recombination deficiency, and a population of platinum-sensitive patients is expected to be homologous recombination deficiency enriched and most likely to benefit from PARP inhibition. Several of these drugs have been studied in ovarian cancer as monotherapy or drug combinations and have demonstrated activity in the recurrent setting, with olaparib, rucaparib, and niraparib achieving U.S. Food and Drug Administration approval with varying indications. (Refer to the Recurrent or Persistent Ovarian Epithelial Cancer, FTC, and PPC Treatment section for more information.) Phase III studies are ongoing with these three agents after first-line treatments, and also with a fourth drug, veliparib, which is not otherwise commercially available.

Information about ongoing clinical trials is available from the NCI website.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献
  1. Hoskins WJ: Surgical staging and cytoreductive surgery of epithelial ovarian cancer. Cancer 71 (4 Suppl): 1534-40, 1993.[PUBMED Abstract]
  2. Hoskins WJ, Bundy BN, Thigpen JT, et al.: The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage III epithelial ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol 47 (2): 159-66, 1992.[PUBMED Abstract]
  3. Hoskins WJ, McGuire WP, Brady MF, et al.: The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Am J Obstet Gynecol 170 (4): 974-9; discussion 979-80, 1994.[PUBMED Abstract]
  4. Bristow RE, Tomacruz RS, Armstrong DK, et al.: Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 20 (5): 1248-59, 2002.[PUBMED Abstract]
  5. Horowitz NS, Miller A, Rungruang B, et al.: Does aggressive surgery improve outcomes? Interaction between preoperative disease burden and complex surgery in patients with advanced-stage ovarian cancer: an analysis of GOG 182. J Clin Oncol 33 (8): 937-43, 2015.[PUBMED Abstract]
  6. Omura GA, Brady MF, Homesley HD, et al.: Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. J Clin Oncol 9 (7): 1138-50, 1991.[PUBMED Abstract]
  7. Armstrong DK, Bundy B, Wenzel L, et al.: Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354 (1): 34-43, 2006.[PUBMED Abstract]
  8. Markman M, Reichman B, Hakes T, et al.: Impact on survival of surgically defined favorable responses to salvage intraperitoneal chemotherapy in small-volume residual ovarian cancer. J Clin Oncol 10 (9): 1479-84, 1992.[PUBMED Abstract]
  9. Markman M: Intraperitoneal chemotherapy. Semin Oncol 18 (3): 248-54, 1991.[PUBMED Abstract]
  10. Levin L, Simon R, Hryniuk W: Importance of multiagent chemotherapy regimens in ovarian carcinoma: dose intensity analysis. J Natl Cancer Inst 85 (21): 1732-42, 1993.[PUBMED Abstract]
  11. McGuire WP, Hoskins WJ, Brady MF, et al.: Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 13 (7): 1589-99, 1995.[PUBMED Abstract]
  12. Bolis G, Favalli G, Danese S, et al.: Weekly cisplatin given for 2 months versus cisplatin plus cyclophosphamide given for 5 months after cytoreductive surgery for advanced ovarian cancer. J Clin Oncol 15 (5): 1938-44, 1997.[PUBMED Abstract]
  13. Alberts DS, Green S, Hannigan EV, et al.: Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol 10 (5): 706-17, 1992.[PUBMED Abstract]
  14. du Bois A, Lück HJ, Meier W, et al.: A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 95 (17): 1320-9, 2003.[PUBMED Abstract]
  15. Neijt JP, Engelholm SA, Tuxen MK, et al.: Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol 18 (17): 3084-92, 2000.[PUBMED Abstract]
  16. Muggia FM, Braly PS, Brady MF, et al.: Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a gynecologic oncology group study. J Clin Oncol 18 (1): 106-15, 2000.[PUBMED Abstract]
  17. The International Collaborative Ovarian Neoplasm Group: Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet 360 (9332): 505-15, 2002.[PUBMED Abstract]
  18. Ozols RF, Bundy BN, Greer BE, et al.: Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 21 (17): 3194-200, 2003.[PUBMED Abstract]
  19. Vasey PA, Jayson GC, Gordon A, et al.: Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 96 (22): 1682-91, 2004.[PUBMED Abstract]
  20. Kristensen GB, Vergote I, Stuart G, et al.: First-line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin. Int J Gynecol Cancer 13 (Suppl 2): 172-7, 2003 Nov-Dec.[PUBMED Abstract]
  21. Bookman MA, Brady MF, McGuire WP, et al.: Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer Intergroup. J Clin Oncol 27 (9): 1419-25, 2009.[PUBMED Abstract]
  22. Hoskins PJ: Triple cytotoxic therapy for advanced ovarian cancer: a failed application, not a failed strategy. J Clin Oncol 27 (9): 1355-8, 2009.[PUBMED Abstract]
  23. Katsumata N, Yasuda M, Takahashi F, et al.: Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet 374 (9698): 1331-8, 2009.[PUBMED Abstract]
  24. Katsumata N, Yasuda M, Isonishi S, et al.: Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. Lancet Oncol 14 (10): 1020-6, 2013.[PUBMED Abstract]
  25. Harano K, Terauchi F, Katsumata N, et al.: Quality-of-life outcomes from a randomized phase III trial of dose-dense weekly paclitaxel and carboplatin compared with conventional paclitaxel and carboplatin as a first-line treatment for stage II-IV ovarian cancer: Japanese Gynecologic Oncology Group Trial (JGOG3016). Ann Oncol 25 (1): 251-7, 2014.[PUBMED Abstract]
  26. Pignata S, Scambia G, Katsaros D, et al.: Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 15 (4): 396-405, 2014.[PUBMED Abstract]
  27. Chan JK, Brady MF, Penson RT, et al.: Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer. N Engl J Med 374 (8): 738-48, 2016.[PUBMED Abstract]
  28. McGuire WP, Hoskins WJ, Brady MF, et al.: Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 334 (1): 1-6, 1996.[PUBMED Abstract]
  29. Mahner S, Burges A: Quality of life as a primary endpoint in ovarian cancer trials. Lancet Oncol 15 (4): 363-4, 2014.[PUBMED Abstract]
  30. Oza AM, Cook AD, Pfisterer J, et al.: Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol 16 (8): 928-36, 2015.[PUBMED Abstract]
  31. Howell SB, Zimm S, Markman M, et al.: Long-term survival of advanced refractory ovarian carcinoma patients with small-volume disease treated with intraperitoneal chemotherapy. J Clin Oncol 5 (10): 1607-12, 1987.[PUBMED Abstract]
  32. Sugarbaker PH: Laboratory and clinical basis for hyperthermia as a component of intracavitary chemotherapy. Int J Hyperthermia 23 (5): 431-42, 2007.[PUBMED Abstract]
  33. Oseledchyk A, Zivanovic O: Intraoperative Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer. Oncology (Williston Park) 29 (9): 695-701, 2015.[PUBMED Abstract]
  34. Alberts DS, Liu PY, Hannigan EV, et al.: Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 335 (26): 1950-5, 1996.[PUBMED Abstract]
  35. Markman M, Bundy BN, Alberts DS, et al.: Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol 19 (4): 1001-7, 2001.[PUBMED Abstract]
  36. Tewari D, Java JJ, Salani R, et al.: Long-term survival advantage and prognostic factors associated with intraperitoneal chemotherapy treatment in advanced ovarian cancer: a gynecologic oncology group study. J Clin Oncol 33 (13): 1460-6, 2015.[PUBMED Abstract]
  37. Jaaback K, Johnson N: Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. Cochrane Database Syst Rev (1): CD005340, 2006.[PUBMED Abstract]
  38. Elit L, Oliver TK, Covens A, et al.: Intraperitoneal chemotherapy in the first-line treatment of women with stage III epithelial ovarian cancer: a systematic review with metaanalyses. Cancer 109 (4): 692-702, 2007.[PUBMED Abstract]
  39. Burger RA, Brady MF, Bookman MA, et al.: Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365 (26): 2473-83, 2011.[PUBMED Abstract]
  40. Perren TJ, Swart AM, Pfisterer J, et al.: A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365 (26): 2484-96, 2011.[PUBMED Abstract]
  41. Bryant HE, Schultz N, Thomas HD, et al.: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434 (7035): 913-7, 2005.[PUBMED Abstract]
  42. Farmer H, McCabe N, Lord CJ, et al.: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434 (7035): 917-21, 2005.[PUBMED Abstract]
  43. Moore K, Colombo N, Scambia G, et al.: Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med 379 (26): 2495-2505, 2018.[PUBMED Abstract]
  44. Vergote I, Tropé CG, Amant F, et al.: Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363 (10): 943-53, 2010.[PUBMED Abstract]
  45. Kehoe S, Hook J, Nankivell M, et al.: Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet 386 (9990): 249-57, 2015.[PUBMED Abstract]
  46. Wright AA, Bohlke K, Armstrong DK, et al.: Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline. Gynecol Oncol 143 (1): 3-15, 2016.[PUBMED Abstract]
  47. Koopman M, Antonini NF, Douma J, et al.: Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet 370 (9582): 135-42, 2007.[PUBMED Abstract]
  48. van Driel WJ, Koole SN, Sikorska K, et al.: Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med 378 (3): 230-240, 2018.[PUBMED Abstract]
  49. Howell SB, Kirmani S, Lucas WE, et al.: A phase II trial of intraperitoneal cisplatin and etoposide for primary treatment of ovarian epithelial cancer. J Clin Oncol 8 (1): 137-45, 1990.[PUBMED Abstract]
  50. Zivanovic O, Abramian A, Kullmann M, et al.: HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer. Int J Cancer 136 (3): 699-708, 2015.[PUBMED Abstract]
  51. Piccart MJ, Bertelsen K, James K, et al.: Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst 92 (9): 699-708, 2000.[PUBMED Abstract]
  52. Verheijen RH, Massuger LF, Benigno BB, et al.: Phase III trial of intraperitoneal therapy with yttrium-90-labeled HMFG1 murine monoclonal antibody in patients with epithelial ovarian cancer after a surgically defined complete remission. J Clin Oncol 24 (4): 571-8, 2006.[PUBMED Abstract]
  53. Pfisterer J, Weber B, Reuss A, et al.: Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO. J Natl Cancer Inst 98 (15): 1036-45, 2006.[PUBMED Abstract]
  54. Berek JS, Taylor PT, Gordon A, et al.: Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer. J Clin Oncol 22 (17): 3507-16, 2004.[PUBMED Abstract]
  55. Stadtmauer EA, O'Neill A, Goldstein LJ, et al.: Phase III randomized trial of high-dose chemotherapy (HDC) and stem cell support (SCT) shows no difference in overall survival or severe toxicity compared to maintenance chemotherapy with cyclophosphamide, methotrexate and 5-fluorourcil (CMF) for women with metastatic breast cancer who are responding to conventional induction chemotherapy: the 'Philadelphia' Intergroup study (PBT-1). [Abstract] Proceedings of the American Society of Clinical Oncology 18: A1, 1a, 1999.[PUBMED Abstract]
  56. Markman M, Liu PY, Wilczynski S, et al.: Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol 21 (13): 2460-5, 2003.[PUBMED Abstract]
  57. Pecorelli S, Favalli G, Gadducci A, et al.: Phase III trial of observation versus six courses of paclitaxel in patients with advanced epithelial ovarian cancer in complete response after six courses of paclitaxel/platinum-based chemotherapy: final results of the After-6 protocol 1. J Clin Oncol 27 (28): 4642-8, 2009.[PUBMED Abstract]
  58. Vergote IB, Jimeno A, Joly F, et al.: Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup study. J Clin Oncol 32 (4): 320-6, 2014.[PUBMED Abstract]
  59. Liu PY, Alberts DS, Monk BJ, et al.: An early signal of CA-125 progression for ovarian cancer patients receiving maintenance treatment after complete clinical response to primary therapy. J Clin Oncol 25 (24): 3615-20, 2007.[PUBMED Abstract]
Recurrent or Persistent Ovarian Epithelial Cancer, FTC, and PPC Treatment

Overall, approximately 80% of patients diagnosed with ovarian epithelial cancer, fallopian tube cancer (FTC), and primary peritoneal cancer (PPC) will relapse after first-line platinum-based and taxane-based chemotherapy and may benefit from subsequent therapies. Early detection of persistent disease by second-look laparotomies after completion of first-line treatment is no longer practiced. When the outcomes in institutions practicing such procedures (50% of institutions) were informally compared with the outcomes in institutions not using such procedures, lack of support for second-look laparotomies grew. This was confirmed in the Gynecologic Oncology Group (GOG) GOG-0158 trial.[ 1 ]

On the other hand, the practice of close follow-up of patients completing treatment by measuring cancer antigen 125 (CA-125) levels at intervals of 1 to 3 months was nearly universally adopted. In patients who are in clinical complete remission, increases in CA-125 from their initial treatment represent the most common method to detect disease that will eventually relapse clinically.

Treatment based on abnormal increases in CA-125 in the absence of symptoms or imaging evidence of disease has been addressed in a clinical trial.

Evidence (early vs. delayed initiation of treatment):

  1. A trial by the Medical Research Council (MRC) (MRC-OV05) and the European Organisation for Research and Treatment of Cancer examined the consequences of early treatment for an elevated CA-125 level versus treatment delayed until clinical symptoms appeared.[ 2 ] Patients in clinical complete remission after platinum-based chemotherapy were registered and followed with CA-125 levels and clinical visits only. Upon detection of a twofold elevation over the normal range, patients were randomly assigned to disclosure of the result and early treatment for recurrence versus continued blinding and treatment upon development of signs and symptoms indicative of clinical relapse. The number of randomly assigned patients was to exceed 500 to yield a superior survival outcome at 2 years with early institution of therapy; this required 1,400 registrations, which were accrued between May 1996 and August 2005.

A quality-of-life assessment accompanying this study found a detrimental effect in the early treatment when it was compared with waiting for the development of signs and symptoms.[ 3 ]

The impact of these findings on CA-125 surveillance patterns over a decade in five U.S. Cancer Centers was disappointingly low.[ 4 ][ 5 ] Monitoring CA-125 levels in follow-up was used to separate platinum-sensitive from platinum-resistant recurrences and plays a role in identifying appropriate candidates for secondary cytoreduction, although this strategy awaits confirmation with a randomized trial.

Treatment Options for Patients with Recurrent or Persistent Ovarian Epithelial Cancer, FTC, and PPC

Treatment options for patients with recurrent disease are subdivided as follows:

  1. Platinum-sensitive recurrence: For patients whose disease recurs more than 6 months after cessation of the induction, re-treatment with a platinum or platinum-containing combination, such as carboplatin, should be considered (refer to Table 8).
  2. Platinum-refractory or platinum-resistant recurrence: For patients who progress before cessation of induction therapy (platinum refractory) or within 6 months after cessation of induction therapy (platinum resistant), platinum therapy is generally not useful as part of the treatment plan. Clinical trials should be considered.

Other agents that have shown activity in phase II trials are listed in Table 10 and may also be used alone or in combination with other drugs, but such treatments are best done in prospective trials.

Cytoreduction may be used;[ 4 ] this intervention is being studied in the setting of a randomized clinical trial (GOG-0213).

The role of radiation therapy in patients with recurrent ovarian cancer has not been defined.

Platinum-sensitive recurrence

Platinum-containing chemotherapy regimens

Table 8 shows the chemotherapy regimens used in first relapse for the treatment of platinum-sensitive recurrent ovarian cancer.

Table 8. Chemotherapy Regimens Used in First Relapse
Eligibility (mo since end of initial therapy) Regimen No. of Patients Comparator Comments on Outcome (mo)
No. = number; OS = overall survival; PFS = progression-free survival.
aTrabectedin has been approved for use in treating recurrent ovarian cancer in Europe and Canada.
bOS data were not mature at the time the manuscript was published.[ ]
cP < .0001.
Most Commonly Used
Platinum sensitive (>6) Cisplatin or carboplatin + paclitaxel 802 Single-agent nontaxane + platinum agents PFS 11 vs. 9; OS 24 vs. 19 [ ]
Platinum sensitive (>6) Carboplatin + gemcitabine 356 Carboplatin PFS 8.6 vs. 5.8; OS 18 vs. 17 [ ]
Platinum sensitive (>6) Carboplatin + pegylated liposomal doxorubicin 976 Carboplatin + paclitaxel PFS 11.3 vs. 9.4; OS 30.7 vs. 33.0 [ ]
Other Regimens
Platinum sensitive (>6) Carboplatin + epirubicin 190 Carboplatin Powered for response differences; OS 17 vs. 15 [ ]
Platinum sensitive (≥12) Cisplatin + doxorubicin + cyclophosphamide 97 Paclitaxel PFS 15.7 vs. 9; OS 34.7 vs. 25.8 [ ]
Platinum sensitive + resistant Pegylated liposomal doxorubicin + trabectedina 672 Pegylated liposomal doxorubicin PFS 7.3 vs. 5.8; OS 20.5 vs. 19.4b
Platinum sensitive Paclitaxel-carboplatin 674 Paclitaxel-carboplatin + bevacizumab PFS 10.4 vs. 13.8c; OS 37.4 vs. 42.2 [ ]

On the basis of improved survival with etoposide or 5-fluorouracil, carboplatin was approved in 1987 for the treatment of patients with ovarian cancer whose disease recurred after treatment with cisplatin.[ 12 ] In a randomized phase II trial of paclitaxel, a currently used second-line drug, the cisplatin-containing combination of cisplatin plus doxorubicin plus cyclophosphamide (CAP), yielded a superior survival outcome.[ 10 ] This study and subsequent studies (see Table 8) have reinforced the use of carboplatin as the treatment core for patients with platinum-sensitive recurrences. Cisplatin is occasionally used, particularly in combination with other drugs, because of its lesser myelosuppression, but this advantage over carboplatin is counterbalanced by greater patient intolerance.

Oxaliplatin, initially introduced with the hope that it would overcome platinum resistance, has activity mostly in platinum-sensitive patients [ 13 ] but has not been compared with carboplatin alone or in combinations.

With all platinum agents, outcome is generally better the longer the initial interval without recurrence from the initial platinum-containing regimens.[ 14 ] Therefore, on occasion, patients with platinum-sensitive recurrences relapsing within 1 year have been included in trials of nonplatinum drugs. In one such trial, comparing the pegylated liposomal doxorubicin to topotecan, the subset of patients who were platinum sensitive had better outcomes with either drug (and in particular with pegylated liposomal doxorubicin) relative to the platinum-resistant cohort.[ 15 ]

Several randomized trials have addressed whether the use of a platinum in combination with other chemotherapy agents is superior to single agents (see Table 8).

Evidence (platinum in combination with other chemotherapy agents):

  1. In an analysis of data examining jointly the results of trials performed by the MRC/Arbeitsgemeinschaft Gynaekologische Onkologie (MRC/AGO) and the International Collaborative Ovarian Neoplasm (ICON) investigators (ICON4), the following results were observed:[ 5 ][ 9 ][Level of evidence: 1iiA]
  2. Another trial by European and Canadian groups compared gemcitabine plus carboplatin with carboplatin.
  3. In a phase III trial, carboplatin plus pegylated liposomal doxorubicin was compared with carboplatin plus paclitaxel in patients with platinum-sensitive recurrence (>6 months). The primary endpoint was PFS.

    Given its toxicity profile and noninferiority to the standard regimen, carboplatin plus pegylated liposomal doxorubicin is an important option for patients with platinum-sensitive recurrence.

Carboplatin plus paclitaxel has been considered the standard regimen for platinum-sensitive recurrence in the absence of residual neurological toxic effects. The GOG-0213 trial is comparing this regimen with the experimental arm that adds bevacizumab to carboplatin plus paclitaxel.

Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy

Evidence (bevacizumab with gemcitabine-carboplatin chemotherapy):

  1. The Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-Angiogenic Therapy in Platinum-Sensitive Recurrent Diseases (OCEANS [NCT00434642]), assessed the role of bevacizumab in the treatment of platinum-sensitive recurrence (see Table 8 for other trials in this setting). In this double-blind, placebo-controlled, phase III trial of chemotherapy (gemcitabine + carboplatin) with or without bevacizumab for recurrent ovarian epithelial cancer, FTC, or PPC, 242 patients were randomly assigned to each arm. In contrast to the first-line studies, treatment was allowed to continue beyond six cycles to ten cycles in responding patients, but there was no maintenance therapy.[ 18 ]

Evidence (bevacizumab with paclitaxel-carboplatin chemotherapy):

  1. NRG Oncology Group, or National Clinical Trials Network (NCTN) group, a combined research effort of the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the GOG (GOG-0213 ([NCT00565851]) assessed both the role of surgical debulking and the addition of bevacizumab induction and maintenance in women with platinum-sensitive recurrences of ovarian cancer.[ 11 ][Level of evidence: 1iiA] The nonsurgical portion of GOG-0213 had 81% power for a true hazard ratio (HR) of 0.75; it enrolled 674 women from December 2007 to August 2011, and the published analysis took place after a median follow-up exceeding 4 years.

Evidence (PARP inhibitors with or without anti-angiogenic agents):

PARP is a family of enzymes involved in base-excision repair of DNA single-strand breaks. In patients with homologous recombination deficiency, including patients with germline BRCA1 or BRCA2 (gBRCA) mutations or with nongermline homologous recombination deficiency–positive tumors, inhibition of PARP results in production of double-strand breaks of DNA. Human DNA repair mechanisms largely rely on one intact copy of the gene; cells with a double-strand break are usually targeted for cell death. This susceptibility of BRCA-deficient or BRCA-mutant cells to PARP inhibition [ 19 ][ 20 ] has spurred the clinical development of this class of agents. Sensitivity to platinum compounds is a feature of homologous recombination deficiency, and a population of platinum-sensitive patients is expected to be homologous recombination deficiency-enriched and most likely to benefit from PARP inhibition.

  1. In a randomized, double blind, placebo-controlled phase II trial of olaparib maintenance therapy, eligible patients had platinum-sensitive, high-grade serous ovarian cancer. Patients were randomly assigned to receive olaparib (400 mg bid) or placebo. Having a gBRCA1 or gBRCA2 mutation was not required for eligibility; however, 23% of patients in the experimental group and 22% of patients in the placebo group had a known BRCA1 or BRCA2 mutation. The primary endpoint was PFS.[ 21 ][Level of evidence: 1iiDiii]
  2. Olaparib tablets (as opposed to the previous capsule formulation) underwent evaluation in SOLO2 (NCT01874353), a double-blind, randomized, placebo-controlled phase III trial in patients with high-grade serous or endometrioid, primary peritoneal, or fallopian tube cancer. Patients had platinum-sensitive relapses and were preselected for BRCA 1/2 mutations.[ 23 ][Level of evidence: 1iiDiii] Stratification for response (complete vs. partial) to previous platinum and platinum-free intervals (>6–12 vs. >12) and 2:1 random allocation to olaparib in two 150-mg twice-daily or matching placebo tablets took place. Of 295 eligible patients enrolled, 196 were assigned to olaparib, and 99 were assigned to a placebo.
  3. Rucaparib underwent phase II evaluation in ARIEL2 (NCT01891344), an open-label study enrolling 206 patients, 204 of whom were actually receiving the drug (192 were actually in classifiable subgroups) and had high-grade platinum-sensitive recurrences between October 2013 and November 2014.[ 25 ][Level of evidence: 3iiDiii] The following three predefined homologous recombination deficiency subgroups on the basis of tumor mutational analysis were studied: The drug was given orally at 600 mg twice daily, and patients were treated until disease progression or other reasons for discontinuation. Median duration of treatment for the 204 patients was 5.7 months.
  4. In a subsequent evaluation, rucaparib was assessed as maintenance therapy after response to platinum therapy in a randomized double-blind, placebo-controlled phase III trial (ARIEL 3 [NCT01968213]).[ 26 ] To be eligible, patients had high-grade carcinomas that were previously treated with at least two platinum-containing regimens and had achieved complete or partial responses to the last platinum-containing regimen. In a 2:1 treatment allocation, from April 2014 to July 2016, 375 patients received rucaparib, and 189 patients received placebo. PFS, as determined by the investigator, was the primary endpoint using a step-down procedure for the following three determined, nested treatment cohorts:Treatment-emergent adverse events of grade 3 or higher in the rucaparib group versus the placebo group consisted primarily of anemia (19% vs. 1%) and increased alanine or aspartate aminotransferases (10% vs. 0%).
  5. Niraparib was evaluated in a double-blind, placebo-controlled phase III trial of 533 patients with platinum-sensitive, predominantly high-grade serous ovarian cancer, who were randomly assigned in a 2:1 ratio to maintenance with oral niraparib or placebo and followed for the primary endpoint of PFS.[ 27 ] Patients were categorized according to the presence or absence of gBRCA or non-BRCA homologous recombination deficiency–positive ovarian cancer or non-BRCA homologous recombination deficiency–negative ovarian cancer, based on BRCA Analysis testing (Myriad Genetics) from tumor and blood samples.
    1. Patients on niraparib had significantly longer median PFS duration compared with a placebo.[ 27 ][Level of evidence: 1iiDiii] Comparisons across categories ranged from HR, 0.27 for gBRCA cancer (21.0 months vs. 5.5 months), HR, 0.38 for non-BRCA cancer, homologous recombination deficiency-positive cancer (12.9 months vs. 3.8 months), and HR, 0.45 for non-BRCA, homologous recombination deficiency-negative cancer (9.3 months vs. 3.9 months).
    2. OS data were not mature at the time of this report, but deaths during the study occurred in 16.1% of patients on niraparib and 19.3% of patients on placebo.
    3. One-third to nearly one-half of the patients had received at least three previous lines of therapy that included the following:
    4. A phase III, randomized, double-blind, placebo-controlled study of niraparib maintenance in patients with homologous recombination deficiency–positive advanced ovarian cancer following response to front-line platinum-based chemotherapy (NCT01847274) is closed to patient accrual and results are pending.
    5. Other PARP inhibitor trials have been exploring their role in platinum-resistant disease and their role in combination with other agents.
  6. Olaparib was also evaluated as a single agent in a multicenter phase II trial for patients with documented germline BRCA1- or BRCA2 mutations.[ 28 ][Level of evidence: 3iiiDiv] This trial was open to patients with platinum-resistant ovarian cancer, breast cancer treated with three or more previous regimens, pancreatic cancer with previously administered gemcitabine, or prostate cancer previously treated with hormonal therapy and one systemic therapy. Olaparib was given at 400 mg twice a day. The primary endpoint was response rate. A total of 298 patients were included.

    The data from this trial were used by the U.S. Food and Drug Administration (FDA) to approve olaparib for patients with ovarian cancer, who have known BRCA1 or BRCA2 mutations and have failed three previous regimens.

  7. Several other trials have combined olaparib with either cytotoxic chemotherapy or other biologic therapy.[ 29 ][ 30 ] Refer to Table 9.

PARP inhibitor trials as maintenance after platinum-based responses are ongoing (refer to Table 9).

Table 9. Olaparib Combinations
Trial Eligibility Arms No. of Patients PFS (mo) OS
AUC = area under the curve; BID = twice a day; g = germline; No. = number; NR = not reported; PFS = progression-free survival; OS = overall survival.
NCT01116648 (2014)[ ] Platinum-sensitive ovarian cancer, either high-grade serous cancer or g BRCA mutation Olaparib 200 mg BID + cediranib 30 mg daily 44 17.7 NR
Olaparib 400 mg BID 46 9.0 NR
NCT01081951 (2015)[ ] Platinum-sensitive, high-grade serous ovarian cancer Olaparib 200 mg BID + paclitaxel 175 mg/m2 + carboplatin AUC 4 81 12.2 NR
Paclitaxel 175 mg/m2 + carboplatin AUC 6 81 9.6 NR

Platinum-refractory or platinum-resistant recurrence

Chemotherapy

Clinical recurrences that take place within 6 months of completion of a platinum-containing regimen are considered platinum-refractory or platinum-resistant recurrences. Anthracyclines (particularly when formulated as pegylated liposomal doxorubicin), taxanes, topotecan, and gemcitabine are used as single agents for these recurrences on the basis of activity and their favorable therapeutic indices relative to agents listed in Table 10. The long list underscores the marginal benefit, if any, of these agents. Clinical trials should be considered for patients with platinum-resistant disease.

Drugs used to treat platinum-refractory or platinum-resistant recurrences include the following:

Chemotherapy and/or bevacizumab

Other drugs used to treat platinum-refractory or platinum-resistant recurrence (efficacy not well defined)

The drugs shown in Table 10 are not fully confirmed to have activity in a platinum-resistant setting, have a less desirable therapeutic index, and have a level of evidence lower than 3iiiDiv.

Table 10. Other Drugs That Have Been Used in the Setting of Recurrent Ovarian Cancer (Efficacy Not Well Defined After Failure of Platinum-Containing Regimens)
Drugs Drug Class Major Toxicities Comments
Etoposide Topoisomerase II inhibitor Myelosuppression; alopecia Oral administration; rare leukemia dampens interest
Cyclophosphamide and several other bis chloroethyl amines Alkylating agents Myelosuppression; alopecia (only the oxazaphosphorines) Leukemia and cystitis; uncertain activity after platinum agents
Hexamethylmelamine (Altretamine) Unknown but probably alkylating prodrugs Emesis and neurologic toxic effects Oral administration; uncertain activity after platinum agents
Irinotecan Topoisomerase I inhibitor Diarrhea and other gastrointestinal symptoms Cross-resistant to topotecan
Oxaliplatin Platinum Neuropathy, emesis, myelosuppression Cross-resistant to usual platinum agents, but less so
Vinorelbine Mitotic inhibitor Myelosuppression Erratic activity
Fluorouracil and capecitabine Fluoropyrimidine antimetabolites Gastrointestinal symptoms and myelosuppression Capecitabine is oral; may be useful in mucinous tumors
Tamoxifen Antiestrogen Thromboembolism Oral administration; minimal activity, perhaps more in subsets

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献
  1. Ozols RF, Bundy BN, Greer BE, et al.: Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 21 (17): 3194-200, 2003.[PUBMED Abstract]
  2. Rustin GJ, van der Burg ME, Griffin CL, et al.: Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet 376 (9747): 1155-63, 2010.[PUBMED Abstract]
  3. Stark DP, Cook A, Brown JM, et al.: Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial. Cancer 123 (14): 2752-2761, 2017.[PUBMED Abstract]
  4. Hoskins WJ, Rubin SC, Dulaney E, et al.: Influence of secondary cytoreduction at the time of second-look laparotomy on the survival of patients with epithelial ovarian carcinoma. Gynecol Oncol 34 (3): 365-71, 1989.[PUBMED Abstract]
  5. Parmar MK, Ledermann JA, Colombo N, et al.: Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet 361 (9375): 2099-106, 2003.[PUBMED Abstract]
  6. Monk BJ, Herzog TJ, Kaye SB, et al.: Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol 28 (19): 3107-14, 2010.[PUBMED Abstract]
  7. Pfisterer J, Plante M, Vergote I, et al.: Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol 24 (29): 4699-707, 2006.[PUBMED Abstract]
  8. Wagner U, Marth C, Largillier R, et al.: Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer 107 (4): 588-91, 2012.[PUBMED Abstract]
  9. Bolis G, Scarfone G, Giardina G, et al.: Carboplatin alone vs carboplatin plus epidoxorubicin as second-line therapy for cisplatin- or carboplatin-sensitive ovarian cancer. Gynecol Oncol 81 (1): 3-9, 2001.[PUBMED Abstract]
  10. Cantù MG, Buda A, Parma G, et al.: Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol 20 (5): 1232-7, 2002.[PUBMED Abstract]
  11. Coleman RL, Brady MF, Herzog TJ, et al.: Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18 (6): 779-791, 2017.[PUBMED Abstract]
  12. Muggia FM: Overview of carboplatin: replacing, complementing, and extending the therapeutic horizons of cisplatin. Semin Oncol 16 (2 Suppl 5): 7-13, 1989.[PUBMED Abstract]
  13. Piccart MJ, Green JA, Lacave AJ, et al.: Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian cancer: A randomized phase II study of the European Organization for Research and Treatment of Cancer Gynecology Group. J Clin Oncol 18 (6): 1193-202, 2000.[PUBMED Abstract]
  14. Markman M, Markman J, Webster K, et al.: Duration of response to second-line, platinum-based chemotherapy for ovarian cancer: implications for patient management and clinical trial design. J Clin Oncol 22 (15): 3120-5, 2004.[PUBMED Abstract]
  15. Gordon AN, Tonda M, Sun S, et al.: Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol 95 (1): 1-8, 2004.[PUBMED Abstract]
  16. Raja FA, Counsell N, Colombo N, et al.: Platinum versus platinum-combination chemotherapy in platinum-sensitive recurrent ovarian cancer: a meta-analysis using individual patient data. Ann Oncol 24 (12): 3028-34, 2013.[PUBMED Abstract]
  17. Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, et al.: Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol 28 (20): 3323-9, 2010.[PUBMED Abstract]
  18. Aghajanian C, Blank SV, Goff BA, et al.: OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30 (17): 2039-45, 2012.[PUBMED Abstract]
  19. Bryant HE, Schultz N, Thomas HD, et al.: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434 (7035): 913-7, 2005.[PUBMED Abstract]
  20. Farmer H, McCabe N, Lord CJ, et al.: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434 (7035): 917-21, 2005.[PUBMED Abstract]
  21. Ledermann J, Harter P, Gourley C, et al.: Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366 (15): 1382-92, 2012.[PUBMED Abstract]
  22. Ledermann J, Harter P, Gourley C, et al.: Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 15 (8): 852-61, 2014.[PUBMED Abstract]
  23. Pujade-Lauraine E, Ledermann JA, Selle F, et al.: Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 18 (9): 1274-1284, 2017.[PUBMED Abstract]
  24. Friedlander M, Gebski V, Gibbs E, et al.: Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial. Lancet Oncol 19 (8): 1126-1134, 2018.[PUBMED Abstract]
  25. Swisher EM, Lin KK, Oza AM, et al.: Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol 18 (1): 75-87, 2017.[PUBMED Abstract]
  26. Coleman RL, Oza AM, Lorusso D, et al.: Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390 (10106): 1949-1961, 2017.[PUBMED Abstract]
  27. Mirza MR, Monk BJ, Herrstedt J, et al.: Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med 375 (22): 2154-2164, 2016.[PUBMED Abstract]
  28. Kaufman B, Shapira-Frommer R, Schmutzler RK, et al.: Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 33 (3): 244-50, 2015.[PUBMED Abstract]
  29. Liu JF, Barry WT, Birrer M, et al.: Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol 15 (11): 1207-14, 2014.[PUBMED Abstract]
  30. Oza AM, Cibula D, Benzaquen AO, et al.: Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol 16 (1): 87-97, 2015.[PUBMED Abstract]
  31. Kohn EC, Sarosy G, Bicher A, et al.: Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer. J Natl Cancer Inst 86 (1): 18-24, 1994.[PUBMED Abstract]
  32. McGuire WP, Rowinsky EK, Rosenshein NB, et al.: Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med 111 (4): 273-9, 1989.[PUBMED Abstract]
  33. Einzig AI, Wiernik PH, Sasloff J, et al.: Phase II study and long-term follow-up of patients treated with taxol for advanced ovarian adenocarcinoma. J Clin Oncol 10 (11): 1748-53, 1992.[PUBMED Abstract]
  34. Thigpen JT, Blessing JA, Ball H, et al.: Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study. J Clin Oncol 12 (9): 1748-53, 1994.[PUBMED Abstract]
  35. Trimble EL, Adams JD, Vena D, et al.: Paclitaxel for platinum-refractory ovarian cancer: results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Center 9103. J Clin Oncol 11 (12): 2405-10, 1993.[PUBMED Abstract]
  36. ten Bokkel Huinink W, Gore M, Carmichael J, et al.: Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol 15 (6): 2183-93, 1997.[PUBMED Abstract]
  37. Gordon AN, Fleagle JT, Guthrie D, et al.: Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 19 (14): 3312-22, 2001.[PUBMED Abstract]
  38. Kudelka AP, Tresukosol D, Edwards CL, et al.: Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma. J Clin Oncol 14 (5): 1552-7, 1996.[PUBMED Abstract]
  39. Creemers GJ, Bolis G, Gore M, et al.: Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study. J Clin Oncol 14 (12): 3056-61, 1996.[PUBMED Abstract]
  40. Bookman MA, Malmström H, Bolis G, et al.: Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol 16 (10): 3345-52, 1998.[PUBMED Abstract]
  41. McGonigle KF, Muntz HG, Vuky J, et al.: Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study. Cancer 117 (16): 3731-40, 2011.[PUBMED Abstract]
  42. Muggia FM, Hainsworth JD, Jeffers S, et al.: Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol 15 (3): 987-93, 1997.[PUBMED Abstract]
  43. Berkenblit A, Seiden MV, Matulonis UA, et al.: A phase II trial of weekly docetaxel in patients with platinum-resistant epithelial ovarian, primary peritoneal serous cancer, or fallopian tube cancer. Gynecol Oncol 95 (3): 624-31, 2004.[PUBMED Abstract]
  44. Friedlander M, Millward MJ, Bell D, et al.: A phase II study of gemcitabine in platinum pre-treated patients with advanced epithelial ovarian cancer. Ann Oncol 9 (12): 1343-5, 1998.[PUBMED Abstract]
  45. Lund B, Hansen OP, Theilade K, et al.: Phase II study of gemcitabine (2',2'-difluorodeoxycytidine) in previously treated ovarian cancer patients. J Natl Cancer Inst 86 (20): 1530-3, 1994.[PUBMED Abstract]
  46. Shapiro JD, Millward MJ, Rischin D, et al.: Activity of gemcitabine in patients with advanced ovarian cancer: responses seen following platinum and paclitaxel. Gynecol Oncol 63 (1): 89-93, 1996.[PUBMED Abstract]
  47. Mutch DG, Orlando M, Goss T, et al.: Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol 25 (19): 2811-8, 2007.[PUBMED Abstract]
  48. Vergote I, Calvert H, Kania M, et al.: A randomised, double-blind, phase II study of two doses of pemetrexed in the treatment of platinum-resistant, epithelial ovarian or primary peritoneal cancer. Eur J Cancer 45 (8): 1415-23, 2009.[PUBMED Abstract]
  49. Miller DS, Blessing JA, Krasner CN, et al.: Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. J Clin Oncol 27 (16): 2686-91, 2009.[PUBMED Abstract]
  50. Pujade-Lauraine E, Hilpert F, Weber B, et al.: Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol 32 (13): 1302-8, 2014.[PUBMED Abstract]
  51. Stockler MR, Hilpert F, Friedlander M, et al.: Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol 32 (13): 1309-16, 2014.[PUBMED Abstract]
  52. Liu JF, Cannistra SA: Emerging role for bevacizumab in combination with chemotherapy for patients with platinum-resistant ovarian cancer. J Clin Oncol 32 (13): 1287-9, 2014.[PUBMED Abstract]
  53. Burger RA, Sill MW, Monk BJ, et al.: Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol 25 (33): 5165-71, 2007.[PUBMED Abstract]
  54. Cannistra SA, Matulonis UA, Penson RT, et al.: Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 25 (33): 5180-6, 2007.[PUBMED Abstract]
  55. Vasey PA, McMahon L, Paul J, et al.: A phase II trial of capecitabine (Xeloda) in recurrent ovarian cancer. Br J Cancer 89 (10): 1843-8, 2003.[PUBMED Abstract]
  56. Monk BJ, Han E, Josephs-Cowan CA, et al.: Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refractory epithelial ovarian cancer. Gynecol Oncol 102 (2): 140-4, 2006.[PUBMED Abstract]
  57. Kaye SB: Bevacizumab for the treatment of epithelial ovarian cancer: will this be its finest hour? J Clin Oncol 25 (33): 5150-2, 2007.[PUBMED Abstract]
  58. Garcia AA, Hirte H, Fleming G, et al.: Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol 26 (1): 76-82, 2008.[PUBMED Abstract]
Changes to This Summary (12/18/2019)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Stage Information for Ovarian Epithelial Cancer, FTC, and PPC

Updated American Joint Committee on Cancer as reference 3.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of ovarian epithelial, fallopian tube, and primary peritoneal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/ovarian/hp/ovarian-epithelial-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389443]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.