Maintenance Therapy for First-Line Treatment of Ovarian Cancer: Is This the Strategy for the Future?

  • Nicoletta Colombo
  • Lucas Minig
  • Robert Burger


The majority of women with epithelial ovarian cancer are diagnosed an advanced stage of disease. Over 70 % of them will experience a relapse of the disease in a mean time of 15 month; only 30–40 % will survive 5 years. Several treatment strategies have been evaluated for prolonging the time free of disease and reducing the risk of death. Maintenance treatment, i.e., continuation of primary chemotherapy in patients without progression of the disease, has been studied with a variety of agents ranging from purely cytotoxic drugs to targeted molecules such as bevacizumab. However, several controversies regarding the impact of maintenance therapy for treating women with ovarian cancer exist. This chapter details the advantages and disadvantages of continuation medical treatment in newly diagnosed ovarian cancer after primary treatment based on the highest levels of evidence.


Ovarian Cancer Maintenance Therapy Epithelial Ovarian Cancer Advanced Ovarian Cancer Recurrent Ovarian Cancer 
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  1. 1.
    Siegel R, De Santis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62:220–41.PubMedCrossRefGoogle Scholar
  2. 2.
    Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.PubMedCrossRefGoogle Scholar
  3. 3.
    Huang L, Cronin KA, Johnson KA, Mariotto AB, Feuer EJ. Improved survival time: what can survival cure models tell us about population-based survival improvements in late-stage colorectal, ovarian, and testicular cancer? Cancer. 2008;112:2289–300.PubMedCrossRefGoogle Scholar
  4. 4.
    Thigpen T. First-line therapy for ovarian carcinoma: what’s next? Cancer Invest. 2004;22 suppl 2:21–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Foster T, Brown TM, Chang J, Menssen HD, Blieden MB, Herzog TJ. A review of the current evidence for maintenance therapy in ovarian cancer. Gynecol Oncol. 2009;115:290–301.PubMedCrossRefGoogle Scholar
  6. 6.
    Jakobsen A, Bertelsen K, Andersen JE, Havsteen H, Jakobsen P, Moeller KA, et al. Dose-effect study of carboplatin in ovarian cancer. J Clin Oncol. 1997;15:193–8.PubMedGoogle Scholar
  7. 7.
    Gore M, Mainwaring P, A’Hern R, MacFarlane V, Slevin M, Harper P, et al. Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. London Gynaecological Oncology Group. J Clin Oncol. 1998;16:2426–34.PubMedGoogle Scholar
  8. 8.
    Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M, et al. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer. J Clin Oncol. 2009;27:1419–25.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Markman M, Liu PY, Moon J, Monk BJ, Copeland L, Wilczynski S, et al. Impact on survival of 12 versus 3 monthly cycles of paclitaxel (175 mg/m2) administered to patients with advanced ovarian cancer who attained a complete response to primary platinum-paclitaxel: follow-up of a Southwest Oncology Group and Gynecologic Oncology Group phase 3 trial. Gynecol Oncol. 2009;14:195–8.CrossRefGoogle Scholar
  10. 10.
    Pecorelli S, Favalli G, Gadducci A, Katsaros D, Panici PB, Carpi A, et al. Phase III trial of observation versus 6 courses of paclitaxel in patients with advanced epithelial ovarian cancer in complete response after 6 courses of paclitaxel/platinum-based chemotherapy. J Clin Oncol. 2009;27:4642–8.PubMedCrossRefGoogle Scholar
  11. 11.
    De Placido S, Scambia G, Di Vagno G, Naglieri E, Lombardi AV, Biamonte R, et al. Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study. J Clin Oncol. 2004;22:2635–42.PubMedCrossRefGoogle Scholar
  12. 12.
    Sauter C, Berchtold W, Fopp M, Gratwohl A, Imbach P, Maurice P, et al. Acute myelogenous leukaemia: maintenance chemotherapy after early consolidation treatment does not prolong survival. Lancet. 1984;1:379–82.PubMedCrossRefGoogle Scholar
  13. 13.
    Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, 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. 2003;21:2460–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Stuart GC, Kitchener H, Bacon M, duBois A, Friedlander M, Ledermann J, et al. 2010 Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer: report from the Fourth Ovarian Cancer Consensus Conference. Int J Gynecol Cancer. 2011;21:750–5.PubMedCrossRefGoogle Scholar
  15. 15.
    A randomized phase III trial of maintenance chemotherapy comparing 12 monthly cycles of single agent paclitaxel or xyotax (CT-2103) (IND# 70177), versus no treatment until documented relapse in women with advanced ovarian or primary peritoneal or fallopian tube cancer who achieve a complete clinical response to primary platinum/taxane chemotherapy, National Cancer Institute NCT00108745. Available from Accessed on Aug 2013.
  16. 16.
    Horwitz SB. Taxol (paclitaxel): mechanisms of action. Ann Oncol. 1994;5 Suppl 6:S3–6.PubMedGoogle Scholar
  17. 17.
    Markman M, Blessing J, Rubin SC, Connor J, Hanjani P, Waggoner S. Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol. 2006;101:436–40.PubMedCrossRefGoogle Scholar
  18. 18.
    Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, 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. 2009;374:1331–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Katsumata NY, Isonishi S, Takahashi F, Michimae H, Kimura E, Aoki D, et al. Long-term follow-up of a randomized trial comparing conventional paclitaxel and carboplatin with dose-dense weekly paclitaxel and carboplatin in women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: JGOG 3016 trial. In: American Society of Clinical Oncology annual meeting, Chicago, 2012.Google Scholar
  20. 20.
    A randomized phase III trial of every-3-weeks paclitaxel versus dose dense weekly paclitaxel in combination with carboplatin with or without concurrent and consolidation bevacizumab (NSC #704865, IND #7921) in the treatment of primary stage II, III or IV epithelial ovarian, peritoneal or fallopian tube cancer, National Cancer Institute NCT01167712. Available from Accessed on Aug 2013.
  21. 21.
    NCCN clinical practice guidelines in oncology – ovarian cancer including fallopian tube cancer and primary peritoneal cancer. 2012. Available from Accessed on Aug 2013.
  22. 22.
    Bertelsen K, Jakobsen A, Strøyer J, Nielsen K, Sandberg E, Andersen JE, et al. A prospective randomized comparison of 6 and 12 cycles of cyclophosphamide, adriamycin, and cisplatin in advanced ovarian cancer: a Danish Ovarian Study Group trial (DACOVA). Gynecol Oncol. 1993;49:30–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Hakes TB, Chalas E, Hoskins WJ, Jones WB, Markman M, Rubin SC, et al. Randomized prospective trial of 5 versus 10 cycles of cyclophosphamide, doxorubicin, and cisplatin in advanced ovarian carcinoma. Gynecol Oncol. 1992;45:284–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Lambert HE, Rustin GJ, Gregory WM, Nelstrop AE. A randomized trial of five versus eight courses of cisplatin or carboplatin in advanced epithelial ovarian carcinoma. A North Thames Ovary Group Study. Ann Oncol. 1997;8:327–33.PubMedCrossRefGoogle Scholar
  25. 25.
    Pfisterer JB, Casado A, Cwiertka K, Pinter T, Pluzanska E, Pujade-Lauraine E, et al. Randomized double-blind placebo-controlled international trial of abagovomab maintenance therapy in patients with advanced ovarian cancer after complete response to first-line chemotherapy: the Monoclonal Antibody Immunotherapy for Malignancies of the Ovary by Subcutaneous Abagovomab (MIMOSA) trial. In: American Society of Clinical Oncology, Chicago, 2011.Google Scholar
  26. 26.
    Browder T, Butterfield CE, Kräling BM, Shi B, Marshall B, O’Reilly MS, et al. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res. 2000;60:1878–86.PubMedGoogle Scholar
  27. 27.
    Bast RC, Thigpen JT, Arbuck SG, Basen-Engquist K, Burke LB, Freedman R, et al. Clinical trial endpoints in ovarian cancer: report of an FDA/ASCO/AACR public workshop. Gynecol Oncol. 2007;107:173–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Donovan KA, Greene PG, Shuster JL, Partridge EE, Tucker DC. Treatment preferences in recurrent ovarian cancer. Gynecol Oncol. 2002;86:200–11.PubMedCrossRefGoogle Scholar
  29. 29.
    Doyle C, Crump M, Pintilie M, Oza AM. Does palliative chemotherapy palliate? Evaluation of expectations, outcomes, and costs in women receiving chemo-therapy for advanced ovarian cancer. J Clin Oncol. 2001;19:1266–74.PubMedGoogle Scholar
  30. 30.
    Calhoun EA, Chang CH, Welshman EE, Fishman DA, Lurain JR, Bennett CL. Evaluating the total costs of chemotherapy-induced toxicity: results from a pilot study with ovarian cancer patients. Oncologist. 2001;6:441–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Burger RA. Overview of anti-angiogenic agents in development for ovarian cancer. Gynecol Oncol. 2011;121:230–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Yoneda J, Kuniyasu H, Crispens MA, Price JE, Bucana CD, Fidler IJ. Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. J Natl Cancer Inst. 1998;90:447–54.PubMedCrossRefGoogle Scholar
  33. 33.
    Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med. 1999;77:527–43.PubMedCrossRefGoogle Scholar
  34. 34.
    Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002;20:4368–80.PubMedCrossRefGoogle Scholar
  35. 35.
    Paley PJ, Staskus KA, Gebhard K, Mohanraj D, Twiggs LB, Carson LF, et al. Vascular endothelial growth factor expression in early stage ovarian carcinoma. Cancer. 1997;80:98–106.PubMedCrossRefGoogle Scholar
  36. 36.
    Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ. Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol. 1995;147:33–41.PubMedCentralPubMedGoogle Scholar
  37. 37.
    Gasparini G, Bonoldi E, Viale G, Verderio P, Boracchi P, Panizzoni GA, et al. Prognostic and predictive value of tumour angiogenesis in ovarian carcinomas. Int J Cancer. 1996;69:205–11.PubMedCrossRefGoogle Scholar
  38. 38.
    Alvarez AA, Krigman HR, Whitaker RS, Dodge RK, Rodriguez GC. The prognostic significance of angiogenesis in epithelial ovarian carcinoma. Clin Cancer Res. 1999;5:587–91.PubMedGoogle Scholar
  39. 39.
    Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007;25:5180–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Burger RA, Sill M, Monk BJ, Greer BE, Sorosky J. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC): a Gynecologic Oncology Group (GOG) study. J Clin Oncol. 2005;23:268.Google Scholar
  41. 41.
    Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al, Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.Google Scholar
  42. 42.
    Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al.; ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.Google Scholar
  43. 43.
    Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, et al. 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. 2012;30:2039–45.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Pujade-Lauraine EH, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, et al. AURELIA: a randomized phase III trial evaluating bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer. In: American Society of Clinical Oncology annual meeting, Chicago, 2012.Google Scholar
  45. 45.
    LUME-Ovar 1: nintedanib (BIBF 1120) or placebo in combination with paclitaxel and carboplatin in first line treatment of ovarian cancer. Available from Accessed on Aug 2013.
  46. 46.
    Efficacy and safety of pazopanib monotherapy after first line chemotherapy in ovarian, fallopian tube, or primary peritoneal cancer. Available from Accessed on Aug 2013.
  47. 47.
    A phase 3 randomized, double-blind, placebo-controlled, multicenter study of AMG 386 with paclitaxel and carboplatin as first-line treatment of subjects with FIGO stage III-IV epithelial ovarian, primary peritoneal or fallopian tube cancers. Available from Accessed on Aug 2013.
  48. 48.
    Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25:5165–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Evaluation of optimal initial treatment duration of bevacizumab in combination with standard chemotherapy in patients with ovarian cancer. Available from Accessed on Aug 2013.
  50. 50.
    Cohn DE, Kim KH, Resnick KE, O’Malley DM, Straughn Jr JM. At what cost does a potential survival advantage of bevacizumab make sense for the primary treatment of ovarian cancer? A cost-effectiveness analysis. J Clin Oncol. 2011;29:1247–51.PubMedCrossRefGoogle Scholar
  51. 51.
    Kristensen G, Perren T, Qian W, Pfisterer J, Ledermann JA, Joly F, et al. Result of interim analysis of overall survival in the GCIG ICON7 phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer. J Clin Oncol. 2011;29(suppl):abstract LBA5006.Google Scholar
  52. 52.
    Arnold DA, Andre T, Bennouna J, Sastre J, Osterlund P, Greil R, et al. Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV + CT: results of a randomised phase III intergroup study – TML (ML18147). In: American Society of Clinical Oncology, Chicago, 2012.Google Scholar
  53. 53.
    Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366:1382–92.PubMedCrossRefGoogle Scholar
  54. 54.
    Oza D, Oaknin Benzaquen A, Poole C, Mathijssen RHJ, Sonke GS, Colombo N, et al. Olaparib plus paclitaxel and carboplatin followed by olaparib maintenance treatment in patients with platinum-sensitive recurrent serous ovarian cancer: a randomized open-label phase II study. In: American Society of Clinical Oncology, Chicago, 2012.Google Scholar
  55. 55.
    Berek J, Taylor P, McGuire W, Smith LM, Schultes B, Nicodemus CF. Oregovomab maintenance monoimmunotherapy does not improve outcomes in advanced ovarian cancer. J Clin Oncol. 2009;27:418–25.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Gynecology OncologyEuropean Institute of OncologyMilanItaly
  2. 2.Gynecology OncologyCentro Integral Oncológico Clara Campal (CIOCC)MadridSpain
  3. 3.Department of Surgical OncologyFox Chase Cancer CenterPhiladelphiaUSA

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