Skip to main content
SpringerLink
Log in

Systemic Induction Chemotherapy for Advanced-Stage Epithelial Ovarian Cancer

  • Chapter
  • First Online:
Induction Chemotherapy

  • 862 Accesses

Abstract

Standard chemotherapy in the management of advanced epithelial ovarian cancer includes a platinum agent (generally carboplatin) and a taxane (generally paclitaxel). Phase 3 trial data have supported the superiority of a weekly dosing schedule for paclitaxel, compared to the “standard” every 3-week drug delivery program, and the addition of an anti-angiogenic agent (bevacizumab). Evidence also supports a potential role for maintenance chemotherapy in this malignancy following the attainment of a maximal response to primary chemotherapy. In addition, phase 3 randomized trial data have revealed that patients with advanced disease managed with a “neoadjuvant treatment approach” (chemotherapy followed by surgery) achieve a similar outcome compared to women who are managed with primary surgical cytoreduction (followed by systemic chemotherapy) but with less morbidity. A number of novel treatment approaches are currently being investigated in ovarian cancer, including several anti-angiogenic agents and PARP inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bateman JC. Chemotherapeutic management of advanced ovarian carcinoma. Med Ann Dist Columbia. 1959;28:537–44.

    CAS  PubMed  Google Scholar 

  2. Kottmeier HL. Treatment of ovarian cancer with thiotepa. Clin Obstet Gynecol. 1968;11:428–38.

    CAS  PubMed  Google Scholar 

  3. Thigpen T, Vance R, Lambuth B, et al. Chemotherapy for advanced or recurrent gynecologic cancer. Cancer. 1987;60:2104–16.

    Article  CAS  PubMed  Google Scholar 

  4. Omura GA, Morrow CP, Blessing JA, et al. A randomized comparison of melphalan versus melphalan plus hexamethylmelamine versus adriamycin plus cyclophosphamide in ovarian carcinoma. Cancer. 1983;51:783–9.

    Article  CAS  PubMed  Google Scholar 

  5. Greene MH, Boice Jr JD, Greer BE, Blessing JA, Dembo AJ. Acute nonlymphocytic leukemia after therapy with alkylating agents for ovarian cancer: a study of five randomized clinical trials: Gynecol Oncol. 1982;307:1416–21.

    Google Scholar 

  6. Travis LB, Curtis RE, Boice Jr JD, Platz CE, Hankey BF, Fraumeni Jr JF. Second malignant neoplasms among long-term survivors of ovarian cancer. Cancer Res. 1996;56:1564–70.

    CAS  PubMed  Google Scholar 

  7. Travis LB, Holowaty EJ, Bergfeldt K, et al. Risk of leukemia after platinum-based chemotherapy for ovarian cancer. N Engl J Med. 1999;340:351–7.

    Article  CAS  PubMed  Google Scholar 

  8. Katz ME, Schwartz PE, Kapp DS, Luikart S. Epithelial carcinoma of the ovary: current strategies. Ann Intern Med. 1981;95:98–111.

    Article  CAS  PubMed  Google Scholar 

  9. Young RC, Chabner BA, Hubbard SP, et al. Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med. 1978;299:1261–6.

    Article  CAS  PubMed  Google Scholar 

  10. Wiltshaw E, Subramarian S, Alexopoulos C, Barker GH. Cancer of the ovary: a summary of experience with cis-dichlorodiammineplatinum(II) at the Royal Marsden Hospital. Cancer Treat Rep. 1979;63:1545–8.

    CAS  PubMed  Google Scholar 

  11. Advanced Ovarian Cancer Trialists Group. Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists’ Group. Br J Cancer. 1998;78:1479–87.

    Google Scholar 

  12. Advanced Ovarian Cancer Trialists Group. Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. Br J Cancer. 1991;303:884–93.

    Google Scholar 

  13. Omura GA, Bundy BN, Berek JS, Curry S, Delgado G, Mortel R. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1989;7:457–65.

    CAS  PubMed  Google Scholar 

  14. 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. 1996;334:1–6.

    Article  CAS  PubMed  Google Scholar 

  15. 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. 2000;92:699–708.

    Article  CAS  PubMed  Google Scholar 

  16. du Bois A, Luck 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. 2003;95:1320–9.

    Article  PubMed  Google Scholar 

  17. 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. 2003;21:3194–200.

    Article  CAS  PubMed  Google Scholar 

  18. 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. 2004;96:1682–91.

    Article  CAS  PubMed  Google Scholar 

  19. Covens A, Carey M, Bryson P, Verma S, Fung Kee FM, Johnston M. Systematic review of first-line chemotherapy for newly diagnosed postoperative patients with stage II, III, or IV epithelial ovarian cancer. Gynecol Oncol. 2002;85:71–80.

    Article  CAS  PubMed  Google Scholar 

  20. 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. 1995;13:1589–99.

    CAS  PubMed  Google Scholar 

  21. Gore M, Mainwaring P, A’Hern R, 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.

    CAS  PubMed  Google Scholar 

  22. Grenman S, Wiklund T, Jalkanen J, et al. A randomised phase III study comparing high-dose chemotherapy to conventionally dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer (FINOVA) study. Eur J Cancer. 2006;42:2196–9.

    Article  CAS  PubMed  Google Scholar 

  23. Schilder RJ, Brady MF, Spriggs D, Shea T. Pilot evaluation of high-dose carboplatin and paclitaxel followed by high-dose melphalan supported by peripheral blood stem cells in previously untreated advanced ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2003;88:3–8.

    Article  CAS  PubMed  Google Scholar 

  24. du Bois A, Weber B, Rochon J, et al. Addition of epirubicin as a third drug to carboplatin-paclitaxel in first-line treatment of advanced ovarian cancer: a prospectively randomized gynecologic cancer intergroup trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens. J Clin Oncol. 2006;24:1127–35.

    Article  PubMed  Google Scholar 

  25. 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. 2009;27:1419–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. 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. 2009;374:1331–8.

    Article  CAS  PubMed  Google Scholar 

  27. Seidman AD, Berry D, Cirrincione C, et al. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008;26:1642–9.

    Article  CAS  PubMed  Google Scholar 

  28. Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008;358:1663–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Miller KD, Sweeney CJ, Sledge Jr GW. Redefining the target: chemotherapeutics as antiangiogenics. J Clin Oncol. 2001;19:1195–206.

    CAS  PubMed  Google Scholar 

  30. 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.

    Article  CAS  PubMed  Google Scholar 

  31. Bertelsen K, Jakobsen A, Stroyer J, et al. A prospective randomized comparison of 6 and 12 cycles of cyclophosphamide, adriamycin, and cisplatin in advanced epithelial ovarian cancer: a Danish Ovarian Study Group trial (DACOVA). Gynecol Oncol. 1993;49:30–6.

    Article  CAS  PubMed  Google Scholar 

  32. Hakes TB, Chalas E, Hoskins WJ, 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.

    Article  CAS  PubMed  Google Scholar 

  33. Markman M, Hakes T, Barakat R, Curtin J, Almadrones L, Hoskins W. Follow-up of Memorial Sloan-Kettering Cancer Center patients treated on National Cancer Institute Treatment Referral Center protocol 9103: paclitaxel in refractory ovarian cancer. J Clin Oncol. 1996;14:796–9.

    CAS  PubMed  Google Scholar 

  34. 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. 2003;21:2460–5.

    Article  CAS  PubMed  Google Scholar 

  35. Markman M, Liu PY, Moon J, 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;114:195–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 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. 2009;27:4642–8.

    Article  CAS  PubMed  Google Scholar 

  37. Markman M, Bookman MA. Second-line treatment of ovarian cancer. Oncologist. 2000;5:26–35.

    Article  CAS  PubMed  Google Scholar 

  38. Dizon DS, Hensley ML, Poynor EA, et al. Retrospective analysis of carboplatin and paclitaxel as initial second-line therapy for recurrent epithelial ovarian carcinoma: application toward a dynamic disease state model of ovarian cancer. J Clin Oncol. 2002;20:1238–47.

    Article  CAS  PubMed  Google Scholar 

  39. The ICON and AGO Collaborators. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003;361:2099–106.

    Article  Google Scholar 

  40. 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. 2006;24:4699–707.

    Article  CAS  PubMed  Google Scholar 

  41. Gore ME, Fryatt I, Wiltshaw E, Dawson T. Treatment of relapsed carcinoma of the ovary with cisplatin or carboplatin following initial treatment with these compounds. Gynecol Oncol. 1990;36:207–11.

    Article  CAS  PubMed  Google Scholar 

  42. Markman M, Rothman R, Hakes T, et al. Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol. 1991;9:389–93.

    CAS  PubMed  Google Scholar 

  43. Vergote I, De Wever I, Tjalma W, Van GM, Decloedt J, van Dam P. Neoadjuvant chemotherapy or primary debulking surgery in advanced ovarian carcinoma: a retrospective analysis of 285 patients. Gynecol Oncol. 1998;71:431–6.

    Article  CAS  PubMed  Google Scholar 

  44. Kuhn W, Rutke S, Spathe K, et al. Neoadjuvant chemotherapy followed by tumor debulking prolongs survival for patients with poor prognosis in International Federation of Gynecology and Obstetrics Stage IIIC ovarian carcinoma. Cancer. 2001;92:2585–91.

    Article  CAS  PubMed  Google Scholar 

  45. Hou JY, Kelly MG, Yu H, et al. Neoadjuvant chemotherapy lessens surgical morbidity in advanced ovarian cancer and leads to improved survival in stage IV disease. Gynecol Oncol. 2007;105:211–7.

    Article  CAS  PubMed  Google Scholar 

  46. Markman M, Belinson J. A rationale for neoadjuvant systemic treatment followed by surgical assessment and intraperitoneal chemotherapy in patients presenting with non-surgically resectable ovarian or primary peritoneal cancers. J Cancer Res Clin Oncol. 2005;131:26–30.

    Article  CAS  PubMed  Google Scholar 

  47. Vergote I, Trope CG, Amant F, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363:943–53.

    Article  CAS  PubMed  Google Scholar 

  48. Burger RA, Sill M, 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.

    Article  CAS  PubMed  Google Scholar 

  49. Cannistra SA. Bevacizumab in patients with advanced platinum-resistant ovarian cancer. J Clin Oncol. 2006;34:5006.

    Google Scholar 

  50. Eskander RN, Tewari K. Incorporation of anti-angiogenesis therapy in the management of advanced ovarian carcinoma- mechanistics, review of phase III randomized clinical trials, and regulatory implications. Gynecol Oncol. 2014;132:496–505.

    Article  CAS  PubMed  Google Scholar 

  51. Bookman MA, Darcy KM, Clarke-Pearson D, Boothby RA, Horowitz IR. Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol. 2003;21:283–90.

    Article  CAS  PubMed  Google Scholar 

  52. Schilder RJ, Sill MW, Chen X, et al. Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a Gynecologic Oncology Group study. Clin Cancer Res. 2005;11:5539–48.

    Article  CAS  PubMed  Google Scholar 

  53. Coleman RL, Broaddus RR, Bodurka DC, et al. Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant epithelial ovarian and primary peritoneal cancers. Gynecol Oncol. 2006;101:126–31.

    Article  CAS  PubMed  Google Scholar 

  54. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.

    Article  CAS  PubMed  Google Scholar 

  55. Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-Ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–34 (published online June 24, 2009).

    Article  CAS  PubMed  Google Scholar 

  56. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–21.

    Article  CAS  PubMed  Google Scholar 

  57. Lederman J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382–92.

    Article  Google Scholar 

  58. Liu JF, Konstantinopoulso PA, Matulonis UA. PARP inhibitors in ovarian cancer: current status and future promise. 2014; 133:362–369.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Treatment Centers of America, Eastern Regional Medical Center, 1331 East Wyoming Avenue, Philadelphia, PA, 19024, USA

    Maurie Markman

Authors
  1. Maurie Markman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maurie Markman .

Editor information

Editors and Affiliations

  1. Department of Surgical Oncology, Medias Klinikum GmbH & Co KG, Burghausen, Germany

    Karl Reinhard Aigner

  2. Royal Prince Alfred, Sydney Hospitals, Mosman, New South Wales, Australia

    Frederick O. Stephens

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Markman, M. (2016). Systemic Induction Chemotherapy for Advanced-Stage Epithelial Ovarian Cancer. In: Aigner, K., Stephens, F. (eds) Induction Chemotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-28773-7_23

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-28773-7_23

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-28771-3

  • Online ISBN: 978-3-319-28773-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation