Skip to main content
SpringerLink
Log in

Primary Chemotherapy and Targeted Molecular Therapy of Epithelial Ovarian Cancer

  • Chapter
  • First Online:
Frontiers in Ovarian Cancer Science

Part of the book series: Comprehensive Gynecology and Obstetrics ((CGO))

  • 960 Accesses

Abstract

The use of paclitaxel in addition to cisplatin resulted in the improvement of ovarian cancer treatment. Based on the results of several randomized clinical trials (RCTs), the combination of paclitaxel and carboplatin administered every 3 weeks intravenously (IV) or a dose-dense regimen of weekly paclitaxel plus carboplatin demonstrates high clinical benefit and has become the standard primary chemotherapy. However, ovarian cancer remains the gynecological cancer with the highest mortality rate despite the establishment of highly effective chemotherapeutic regimens. One strategy to obtain further chemotherapeutic efficacy in the primary treatment of advanced ovarian cancer is neoadjuvant chemotherapy (NAC), and another is intraperitoneal (IP) chemotherapy. NAC is gaining acceptance in cases in which complete resection is not possible with only primary debulking surgery. IP therapy has been reported to be superior to conventional IV chemotherapy; on the other hand, there are complications specific to IP therapy. Several RCTs are currently underway to address these issues. In recent years, molecularly targeted drugs have been widely used in cancer treatment, and they currently play major roles in the treatment of ovarian cancer. In this article, the molecularly targeted therapy used in initial chemotherapy and subsequent maintenance therapy for ovarian cancer will be discussed.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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. Piver S, Barlow JJ, Chung WS, Lee FT, Vongtama V. Primary treatment of advanced ovarian adenocarcinoma, stages III and IV. Natl Cancer Inst Monogr. 1975;42:177–82.

    CAS  PubMed  Google Scholar 

  2. Fisher RI, Young RC. Advances in the staging and treatment of ovarian cancer. Cancer. 1977;39:967–72.

    Article  CAS  PubMed  Google Scholar 

  3. Omura G, Blessing JA, Ehrlich CE, Miller A, Yordan E, Creasman WT, Homesley HD. A randomized trial of cyclophosphamide and doxorubicin with or without cisplatin in advanced ovarian carcinoma. Cancer. 1986;57:1725–30.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  CAS  PubMed  Google Scholar 

  5. McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, et al. Cyclophosphamide and cisplatin versus paclitaxel and cisplatin: a phase III randomized trial in patients with suboptimal stage III/IV ovarian cancer (from the Gynecologic Oncology Group). Semin Oncol. 1996;23:40–7.

    CAS  PubMed  Google Scholar 

  6. Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, 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 

  7. Alberts DS, Green S, Hannigan EV, O’Toole R, Stock-Novack D, Anderson P, 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. 1992;10:706–17.

    Google Scholar 

  8. Swenerton K, Jeffrey J, Stuart G, Roy M, Krepart G, Carmichael J, et al. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1992;10:718–26.

    Article  CAS  PubMed  Google Scholar 

  9. Neijt JP, Engelholm SA, Tuxen MK, Sorensen PG, Hansen M, Sessa C, et al. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol. 2000;18:3084–92.

    Article  CAS  PubMed  Google Scholar 

  10. du Bois A, Lück HJ, Meier W, Adams HP, Möbus V, Costa S, 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 

  11. Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, 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 

  12. Ovarian Cancer (Version 1. 2016) NCCN Clinical Practice Guidelines in Oncology https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#ovarian

  13. Komiyama S, Katabuchi H, Mikami M, Nagase S, Okamoto A, Ito K, Morishige K, Suzuki N, Kaneuchi M, Yaegashi N, Udagawa Y, Yoshikawa H. Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer. Int J Clin Oncol. 2016;21:435–46.

    Article  PubMed  Google Scholar 

  14. Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C, ESMO Guidelines Working Group. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi24–32.

    Article  PubMed  Google Scholar 

  15. ten Bokkel HW, Lane SR, Ross GA, International Topotecan Study Group. Long-term survival in a phase III, randomised study of topotecan versus paclitaxel in advanced epithelial ovarian carcinoma. Ann Oncol. 2004;15:100–3.

    Article  Google Scholar 

  16. Gordon AN, Tonda M, Sun S, Rackoff W, Doxil Study 30–49 Investigators. 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. 2004;95:1–8.

    Article  CAS  PubMed  Google Scholar 

  17. 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: a Phase III Trial of the Gynecologic Cancer Intergroup. J Clin Oncol. 2009;27:1419–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Vermorken JB, Kobierska A, van der Burg ME, Chevallier B, Zanaboni F, ten Bokkel Huinink WW, et al. High-dose epirubicin in platinum-pretreated patients with ovarian carcinoma: the EORTC-GCCG experience. Eur J Gynaecol Oncol. 1995;16:433–8.

    CAS  PubMed  Google Scholar 

  19. du Bois A, Lück HJ, Bauknecht T, Meier W, Richter B, Kuhn W, et al. First-line chemotherapy with epirubicin, paclitaxel, and carboplatin for advanced ovarian cancer: a phase I/II study of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group. J Clin Oncol. 1999;17:46–51.

    Article  PubMed  Google Scholar 

  20. du Bois A, Weber B, Rochon J, Meier W, Goupil A, Olbricht S, 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.

    Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

  22. Katsumata N, Yasuda M, Isonishi S, Takahashi F, Michimae H, Kimura E, 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. 2013;14:1020–6.

    Article  CAS  PubMed  Google Scholar 

  23. Pignata S, Scambia G, Katsaros D, Gallo C, Pujade-Lauraine E, De Placido S, 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. 2014;15:396–405.

    Article  CAS  PubMed  Google Scholar 

  24. Markman M, Zanotti K, Webster K, Peterson G, Kulp B, Belinson J. Phase 2 trial of single agent docetaxel in platinum and paclitaxel-refractory ovarian cancer, fallopian tube cancer, and primary carcinoma of the peritoneum. Gynecol Oncol. 2003;91:573–6.

    Article  CAS  PubMed  Google Scholar 

  25. Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, 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 

  26. Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E, et al. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol. 2011;29:3628–35.

    Article  CAS  PubMed  Google Scholar 

  27. Monga M, Carmichael JA, Shelley WE, Kirk ME, Krepart GV, Jeffrey JF, Pater JL. Surgery without adjuvant chemotherapy for early epithelial ovarian carcinoma after comprehensive surgical staging. Gynecol Oncol. 1991;43:195–7.

    Article  CAS  PubMed  Google Scholar 

  28. Young RC, Walton LA, Ellenberg SS, Homesley HD, Wilbanks GD, Decker DG, et al. Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials. N Engl J Med. 1990;322:1021–7.

    Article  CAS  PubMed  Google Scholar 

  29. Trimbos JB, Vergote I, Bolis G, Vermorken JB, Mangioni C, Madronal C, 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. Natl Cancer Inst. 2003;95:113–25.

    Article  CAS  Google Scholar 

  30. Colombo N, Guthrie D, Chiari S, Parmar M, Qian W, Swart AM, 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. 2003;95:125–32.

    Article  PubMed  Google Scholar 

  31. Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, 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. Natl Cancer Inst. 2003;95:105–12.

    Article  Google Scholar 

  32. Winter-Roach BA, Kitchener HC, Lawrie TA. Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer. Cochrane Database Syst Rev. 2012;3:CD004706. Review. Update in: Cochrane Database Syst Rev. 2015; (12): CD004706

    PubMed Central  Google Scholar 

  33. Sugiyama T, Kamura T, Kigawa J, Terakawa N, Kikuchi Y, Kita T, et al. Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer. 2000;88:2584–9.

    Article  CAS  PubMed  Google Scholar 

  34. Hess V, A’Hern R, Nasiri N, King DM, Blake PR, Barton DP, et al. Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment. J Clin Oncol. 2004;22:1040–4.

    Google Scholar 

  35. Itamochi H, Kigawa J, Sultana H, Iba T, Akeshima R, Kamazawa S, et al. Sensitivity to anticancer agents and resistance mechanisms in clear cell carcinoma of the ovary. Jpn J Cancer Res. 2002;93:723–8.

    Article  CAS  PubMed  Google Scholar 

  36. Sugiyama T, Okamoto A, Enomoto T, Hamano T, Aotani E, Terao Y, et al. Randomized Phase III Trial of Irinotecan Plus Cisplatin Compared With Paclitaxel Plus Carboplatin As First-Line Chemotherapy for Ovarian Clear Cell Carcinoma:JGOG3017/GCIG Trial. J Clin Oncol. 2016;34:2881–7.

    Article  CAS  PubMed  Google Scholar 

  37. Temsirolimus, Carboplatin, and Paclitaxel as First-Line Therapy in Treating Patients With Newly Diagnosis Stage III/IV Clear Cell Ovarian Cancer (NCT01195429). http://clinicaltrials.gov/show/NCT01196429

  38. Seidman JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol. 2003;27:985–93.

    Article  PubMed  Google Scholar 

  39. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474:609–15.

    Article  Google Scholar 

  40. Jarboe EA, Folkins AK, Drapkin R, Ince TA, Agoston ES, Crum CP. Tubal and ovarian pathways to pelvic epithelial cancer: a pathological perspective. Histopathology. 2009;55:619.

    Article  PubMed  Google Scholar 

  41. Yang W, Soares J, Greninger P, Edelman EJ, Lightfoot H, Forbes S, et al. Genomics of drug Sensitivity in cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 2013;41(Database issue):D955–61.

    Article  CAS  PubMed  Google Scholar 

  42. Kuhn W, Rutke S, Spathe K, Schmalfeldt B, Florack G, von Hundelshausen B, 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 

  43. Lee SJ, Kim BG, Lee JW, Park CS, Lee JH, Bae DS. Preliminary results of neoadjuvant chemo therapy with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who are inadequate for optimum primary surgery. J Obsret Gynaecol Res. 2006;32:99–106.

    Article  CAS  Google Scholar 

  44. Hegazy MA, Hegazi RA, Elshafei MA, Setit AE, Elshamy MR, Eltaroongy M, et al. Neoadjuvant chemotherapy versus primary surgery in advanced ovarian carcinoma. World J Surg Oncol. 2005;3:57.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Giannopoulos T, Butler-Ylanuel S, Taylor A, Ngeh N, Thomas H. Clinical outcomes of neoadjuvant chemotherapy and primary debulking surgery in advanced ovarian carcinoma. Eur J Gynaecol Oncol. 2006;27:25–8.

    CAS  PubMed  Google Scholar 

  46. Chan YM, Ng TY, Ngan HY, Wong LC. Quality of life in women treated with neoadjuvant chemotherapy for advanced ovarian cancer: a prospective longitudinal study. Gynecol Oncol. 2003;88:9–16.

    Article  CAS  PubMed  Google Scholar 

  47. Bristow RE, Chi DS. Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis. Gynecol Oncol. 2006;103:1070–6.

    Article  CAS  PubMed  Google Scholar 

  48. Kang S, Nam BH. Does neoadjuvant chemotherapy increase optimal cytoreduction rate in advanced ovarian cancer ? Meta-analysis of 21 studies. Ann Surg Oncol. 2009;16:2315–20.

    Article  PubMed  Google Scholar 

  49. Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, 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 

  50. Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015;386:249–57.

    Article  PubMed  Google Scholar 

  51. Onda T, Satoh T, Saito T, Kasamatsu T, Nakanishi T, Nakamura K, et al. Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602. Eur J Cancer. 2016;64:22–31.

    Article  PubMed  Google Scholar 

  52. Aletti GD, Eisenhauer EL, Santillan A, Axtell A, Aletti G, Holschneider C, et al. Identification of patient groups at highest risk from traditional approach to ovarian cancer treatment. Gynecol Oncol. 2011;120:23–8.

    Article  PubMed  Google Scholar 

  53. Wright JD, Lewin SN, Deutsch I, Burke WM, Sun X, Neugut AI, et al. Defining the limits of radical cytoreductive surgery for ovarian cancer. Gynecol Oncol. 2011;123:467–73.

    Article  PubMed  Google Scholar 

  54. Thrall MM, Goff BA, Symons RG, Flum DR, Gray HJ. Thirty-day mortality after primary cytoreductive surgery for advanced ovarian cancer in the elderly. Obstet Gynecol. 2011;118:537–47.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Thrall MM, Gray HJ, Symons RG, Weiss NS, Flum DR, Goff BA. Neoadjuvant chemotherapy in the Medicare cohort with advanced ovarian cancer. Gynecol Oncol. 2011;123:461–6.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Rauh-Hain JA, Rodriguez N, Growdon WB, Goodman AK, Boruta DM 2nd, Horowitz NS, et al. Primary debulking surgery versus neoadjuvant chemotherapy in stage IV ovarian cancer. Ann Surg Oncol. 2012;19:959–65.

    Article  PubMed  Google Scholar 

  57. Howell SB, Pfeifle CL, Wung WE, Olshen RA, Lucas WE, Yon JL, et al. Intraperitoneal cisplatin with systemic thiosulfate protection. Ann Intern Med. 1982;97:845–51.

    Article  CAS  PubMed  Google Scholar 

  58. Braly PS, McClay EF, Saltzstein SL, Plaxe SC, Kim S, et al. A comparison of intravenous versus intraperitoneal chemotherapy for the initial treatment of ovarian cancer. Gynecol Oncol. 1994;54:338–44.

    Article  PubMed  Google Scholar 

  59. Alberts DS, Liu PY, Hannigan EV, O’Toole R, Williams SD, Young JA, et al. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996;335:1950–5.

    Article  CAS  PubMed  Google Scholar 

  60. Polyzos A, Tasvaris N, Kosmas C, Giannikos L, Katsikas M, Kalahanis N, et al. A comparative study of intraperitoneal carboplatin versus intravenous carboplatin with intravenous cyclophosphamide in both arms as initial chemotherapy for stage III ovarian cancer. Oncology. 1999;56:291–6.

    Article  CAS  PubMed  Google Scholar 

  61. Gadducci A, Carnino F, Chiara S, Brunetti I, Tanganelli L, Romanini A, et al. Intraperitoneal versus intravenous cisplatin in combination with intravenous cyclophosphamide and epidoxorubicin in optimally cytoreduced advanced epithelial ovarian cancer : a randomized trial of the Gruppo Oncologica Nord Ovest. Gynecol Oncol. 2000;76:157–62.

    Article  CAS  PubMed  Google Scholar 

  62. Yen MS, Juang CM, Lai CR, Chao GC, Ng HT, Yuan CC. Intraperitoneal cisplatin-based chemotherapy vs. intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancer. Int J Gynaecol Obstet. 2001;72:55–60.

    Article  CAS  PubMed  Google Scholar 

  63. Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, 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. 2001;19:1101–7.

    Google Scholar 

  64. Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34–43.

    Article  CAS  PubMed  Google Scholar 

  65. NCI Clinical Announcement on Intraperitoneal Chemotherapy in Ovarian Cancer. 2006. https://ctep.cancer.gov/highlights/20060105_ovarian.htm

  66. Alberts DS, Markman M, Muggia F, Ozols RF, Eldermire E, Bookman MA, et al. Proceedings of a GOG workshop on intraperitoneal therapy for ovarian cancer. Gynecol Oncol. 2006;103:783–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Tewari D, Java JJ, Salani R, Armstrong DK, Markman M, Herzog T, 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. 2015;33:1460–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Fujiwara K, Aotani E, Hamano T, Nagao S, Yoshikawa H, Sugiyama T, et al. A randomized phase II/III trial of 3 weekly intraperitoneal versus intravenous carboplatin in combination with intravenous weekly dose-dense paclitaxel for newly diagnosed ovarian, fallopian tube and primary peritoneal cancer. Jpn J Clin Oncol. 2011;41:278–82.

    Article  PubMed  Google Scholar 

  69. Mackay HJ, Provencheur D, Heywood M, Tu D, Eisenhauer EA, Oza AM, et al. Phase II/III study of intraperitoneal chemotherapy after neoadjuvant chemotherapy for ovarian cancer: ncic ctg ov.21. Curr Oncol. 2011;18:84–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Graybill W, Sood AK, Monk BJ, Coleman RL. State of the science: emerging therapeutic strategies for targeting angiogenesis in ovarian cancer. Gynecol Oncol. 2015;138:223–6.

    Article  PubMed  Google Scholar 

  71. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.

    Article  CAS  PubMed  Google Scholar 

  72. Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.

    Article  CAS  PubMed  Google Scholar 

  73. Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. Bevacizumab combined wi出 chemotherapy for platinum-resistant recurrent ovarian cancer : the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32:1302–8.

    Article  CAS  PubMed  Google Scholar 

  74. 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.

    Article  CAS  PubMed  Google Scholar 

  75. du Bois A, Kristensen G, Ray-Coquard I, Reuss A, Pignata S, Colombo N, et al. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2016;17:78–89.

    Article  CAS  PubMed  Google Scholar 

  76. du Bois A, Floquet A, Kim JW, Rau J, del Campo JM, Friedlander M, et al. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol. 2014;32:3374–82.

    Article  PubMed  Google Scholar 

  77. Kim MK, Seong SJ, Kim JW, Bae DS, Jeon S, Kwon SH, et al. Management of endometrial hyperplasia: a survey of members of the Korean Gynecologic Oncology Group. Int J Gynecol Cancer. 2015;25:1277–84.

    Article  PubMed  Google Scholar 

  78. Amé JC, Rolli V, Schreiber V, Niedergang C, Apiou F, Decker P, et al. PARP-2, a novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J Biol Chem. 1999;274:17860–8.

    Article  PubMed  Google Scholar 

  79. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–7.

    Article  CAS  PubMed  Google Scholar 

  80. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, 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 

  81. 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.

    Article  CAS  PubMed  Google Scholar 

  82. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, 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 randomized phase 2 trial. Lancet Oncol. 2014;15:852–61.

    Article  CAS  PubMed  Google Scholar 

  83. Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016;17:1579–1589.

    Article  CAS  PubMed  Google Scholar 

  84. Coleman RL, Sill MW, Bell-McGuinn K, Aghajanian C, Gray HJ, Tewari KS, et al. A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation - an NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2015;137:386–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics & Gynecology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan

    Satoru Nagase M.D., Ph.D., Tsuyoshi Ohta M.D., Ph.D. & Manabu Seino M.D., Ph.D.

Authors
  1. Satoru Nagase M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tsuyoshi Ohta M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manabu Seino M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Satoru Nagase M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Obstetrics and Gynecology, Kumamoto University, Kumamoto, Japan

    Hidetaka Katabuchi

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Nagase, S., Ohta, T., Seino, M. (2017). Primary Chemotherapy and Targeted Molecular Therapy of Epithelial Ovarian Cancer. In: Katabuchi, H. (eds) Frontiers in Ovarian Cancer Science. Comprehensive Gynecology and Obstetrics. Springer, Singapore. https://doi.org/10.1007/978-981-10-4160-0_12

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-4160-0_12

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-4159-4

  • Online ISBN: 978-981-10-4160-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation