Stage III and Stage IV Ovarian Epithelial Cancer Treatment
Table 2. Paclitaxel/Platinum Combinations Versus Comparator Arms in Trials continued...
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. A subsequent analysis will appear when additional survival data become mature; however, at the time of publication, differences in median survival were not apparent, and crossover from a placebo to bevacizumab had occurred in 31% of the patients. Bevacizumab-associated toxicities such as hypertension and proteinuria were more prominent than in the first-line trials, but feared safety issues, such as gastrointestinal perforations, did not occur during the study. Discontinuing treatment because of adverse events was more common with bevacizumab (n = 55 vs. n = 12 for placebo) but fewer patients discontinued treatment because of disease progression (n = 104 vs. n = 160 for placebo).[Level of evidence: 1iiDiii]
These three studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab and chemotherapy combination was extended beyond six cycles until progression. Without additional data, a statement about how bevacizumab should be used in ovarian cancer treatment is not possible because of the uncertain impact on OS, lack of clear delineation of who derives the greatest benefit, and prominent, associated toxicities.
At this time, 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.
Treatment Options Under Clinical Evaluation
- Additional IP radioimmunoconjugates, vaccines, and targeted drugs are under clinical evaluation, primarily as consolidation therapy.
Information about ongoing clinical trials is available from the NCI Web site.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III ovarian epithelial cancer and stage IV ovarian epithelial cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Hoskins WJ: Surgical staging and cytoreductive surgery of epithelial ovarian cancer. Cancer 71 (4 Suppl): 1534-40, 1993.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Armstrong DK, Bundy B, Wenzel L, et al.: Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354 (1): 34-43, 2006.
- 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.
- Jaaback K, Johnson N: Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. Cochrane Database Syst Rev (1): CD005340, 2006.
- van der Burg ME, van Lent M, Buyse M, et al.: The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med 332 (10): 629-34, 1995.
- Goodman HM, Harlow BL, Sheets EE, et al.: The role of cytoreductive surgery in the management of stage IV epithelial ovarian carcinoma. Gynecol Oncol 46 (3): 367-71, 1992.
- 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.
- Markman M: Intraperitoneal chemotherapy. Semin Oncol 18 (3): 248-54, 1991.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Hoskins PJ: Triple cytotoxic therapy for advanced ovarian cancer: a failed application, not a failed strategy. J Clin Oncol 27 (9): 1355-8, 2009.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- McGuire WP: Maintenance therapy for ovarian cancer: of Helsinki and Hippocrates. J Clin Oncol 27 (28): 4633-4, 2009.
- 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.
- 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.
- 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.
- Muggia F: Bevacizumab in ovarian cancer: unanswered questions. Drugs 72 (7): 931-6, 2012.