Skip to main content

Treatment of Recurrent Epithelial Ovarian Cancer

  • Chapter
  • First Online:
Frontiers in Ovarian Cancer Science

Abstract

Recurrent ovarian cancer (ROC) treatment is drawing attention and treatment strategies appear to be changing. Although an average response rate of 70% was achieved in initial treatment through aggressive operations leading to optimal resection followed by chemotherapy, most patients in advanced disease stages recurred within 2 years. Multiple-line clinical trials, including newly proposed targeted therapies, are ongoing and are steadily proving positive survival outcomes. Thus, the role of secondary cytoreductive surgery is being reassessed accordingly. The goal of treatment in ROC is prolonged survival without decreasing quality of life. In the near future, there may be a chance to expect the treatment leading to complete cure in ROC. However, the financial burden of continually increasing prices suffers patients with the expectancy of life prolongation. Besides costs, treatment choices of ROC should consider complex factors such as platinum agent efficacy, germline mutation, drug toxicities, disease spread, and treatment convenience. Finally, treatment of recurrence should be individually tailored to each patient with the intention of securing a high quality of life.

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

Access this chapter

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. Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, et al. Carcinoma of the ovary. FIGO 26th Annual Report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet. 2006;95(Suppl 1):S161–92.

    Article  PubMed  Google Scholar 

  2. Saito T, Katabuchi H. Annual Report of the Committee on Gynecologic Oncology, Japan Society of Obstetrics and Gynecology: Patient Annual Report for 2013 and Treatment Annual Report for 2008. J Obstet Gynaecol Res. 2016;42:1069–79.

    Article  PubMed  Google Scholar 

  3. Ozols RF. Systemic therapy for ovarian cancer: current status and new treatments. Semin Oncol. 2006;33(2 Suppl 6):S3–11.

    Article  CAS  PubMed  Google Scholar 

  4. Colombo N, Gore M. Treatment of recurrent ovarian cancer relapsing 6-12 months post platinum-based chemotherapy. Crit Rev Oncol Hematol. 2007;64:129–38.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Markman M, Markman J, Webster K, Zanotti K, Kulp B, Peterson G, 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. 2004;22:3120–5.

    Article  CAS  PubMed  Google Scholar 

  7. Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, 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. 2003;361:2099–106.

    Article  CAS  PubMed  Google Scholar 

  8. Pfisterer J, Vergote I, Du Bois A, Eisenhauer E, Ago O, Ncic CTG, et al. Combination therapy with gemcitabine and carboplatin in recurrent ovarian cancer. Int J Gynecol Cancer. 2005;15(Suppl 1):36–41.

    Article  PubMed  Google Scholar 

  9. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.

    Article  PubMed  Google Scholar 

  10. Matulonis UA, Oza AM, Ho TW, Ledermann JA. Intermediate clinical endpoints: a bridge between progression-free survival and overall survival in ovarian cancer trials. Cancer. 2015;121:1737–46.

    Article  PubMed  Google Scholar 

  11. Lee CK, Lord S, Grunewald T, Gebski V, Hardy-Bessard AC, Sehouli J, et al. Impact of secondary cytoreductive surgery on survival in patients with platinum sensitive recurrent ovarian cancer: analysis of the CALYPSO trial. Gynecol Oncol. 2015;136:18–24.

    Article  PubMed  Google Scholar 

  12. Bristow RE, Puri I, Chi DS. Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol. 2009;112:265–74.

    Article  PubMed  Google Scholar 

  13. (Guidelines) National Comprehensive Cancer Network (NCCN). Ovarian cancer including fallopian tube cancer and primary peritoneal cancer. 2016.

    Google Scholar 

  14. Gonzalez-Martin AJ, Calvo E, Bover I, Rubio MJ, Arcusa A, Casado A, et al. Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study. Ann Oncol. 2005;16:749–55.

    Article  CAS  PubMed  Google Scholar 

  15. Komiyama S, Katabuchi H, Mikami M, Nagase S, Okamoto A, Ito K, et al. 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 

  16. Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, 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. 2010;28:3323–9.

    Article  CAS  PubMed  Google Scholar 

  17. Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, 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. 2012;107:588–91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Nakanishi T, Aoki D, Watanabe Y, Ando Y, Tomotsugu N, Sato Y, et al. A Phase II clinical trial of pegylated liposomal doxorubicin and carboplatin in Japanese patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer. Jpn J Clin Oncol. 2015;45:422–6.

    Article  PubMed  Google Scholar 

  19. Alberts DS, Liu PY, Wilczynski SP, Clouser MC, Lopez AM, Michelin DP, et al. Randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy (Southwest Oncology Group Protocol S0200). Gynecol Oncol. 2008;108:90–4.

    Article  CAS  PubMed  Google Scholar 

  20. Poveda A, Vergote I, Tjulandin S, Kong B, Roy M, Chan S, et al. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial. Ann Oncol. 2011;22:39–48.

    Article  CAS  PubMed  Google Scholar 

  21. Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, et al. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010;28:3107–14.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. Gadducci A, Lanfredini N, Sergiampietri C. Antiangiogenic agents in gynecological cancer: State of art and perspectives of clinical research. Crit Rev Oncol Hematol. 2015;96:113–28.

    Article  PubMed  Google Scholar 

  24. Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, 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. 2012;30:2039–45.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015;139:10–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. 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 randomised phase 2 trial. Lancet Oncol. 2014;15:852–61.

    Article  CAS  PubMed  Google Scholar 

  27. 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;17:1579–89.

    Article  CAS  PubMed  Google Scholar 

  28. Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015;16:87–97.

    Article  CAS  PubMed  Google Scholar 

  29. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33:244–50.

    Article  CAS  PubMed  Google Scholar 

  30. Fong PC, Yap TA, Boss DS, Carden CP, Mergui-Roelvink M, Gourley C, et al. Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol. 2010;28:2512–9.

    Article  CAS  PubMed  Google Scholar 

  31. Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010;376:245–51.

    Article  CAS  PubMed  Google Scholar 

  32. Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011;12:852–61.

    Article  CAS  PubMed  Google Scholar 

  33. Kaye SB, Lubinski J, Matulonis U, Ang JE, Gourley C, Karlan BY, et al. Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J Clin Oncol. 2012;30:372–9.

    Article  CAS  PubMed  Google Scholar 

  34. 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 

  35. 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 Central  PubMed  Google Scholar 

  36. Drew Y, Ledermann J, Hall G, Rea D, Glasspool R, Highley M, et al. Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer. Br J Cancer. 2016;114:723–30.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Kummar S, Oza AM, Fleming GF, Sullivan DM, Gandara DR, Naughton MJ, et al. Randomized trial of oral cyclophosphamide and Veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer. Clin Cancer Res. 2015;21:1574–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014;15:1207–14.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, et al. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2013;14:882–92.

    Article  CAS  PubMed  Google Scholar 

  40. Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 2016375:2154–164

    Google Scholar 

  41. Horowitz NS, Miller A, Rungruang B, Richard SD, Rodriguez N, Bookman MA, 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. 2015;33:937–43.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Onda T, Yoshikawa H, Yasugi T, Yamada M, Matsumoto K, Taketani Y. Secondary cytoreductive surgery for recurrent epithelial ovarian carcinoma: proposal for patients selection. Br J Cancer. 2005;92:1026–32.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Plotti F, Scaletta G, Aloisi A, Luvero D, Capriglione S, Miranda A, et al. Quality of life in platinum-sensitive recurrent ovarian cancer: chemotherapy versus surgery plus chemotherapy. Ann Surg Oncol. 2015;22:2387–94.

    Article  PubMed  Google Scholar 

  44. Ushijima K, Kamura T, Tamura K, Kuzuya K, Sugiyama T, Noda K, et al. Docetaxel/irinotecan combination chemotherapy in platinum/taxane-refractory and -resistant ovarian cancer: JGOG/WJGOG Intergroup Study. Int J Clin Oncol. 2013;18:126–31.

    Article  CAS  PubMed  Google Scholar 

  45. Brewer CA, Blessing JA, Nagourney RA, Morgan M, Hanjani P. Cisplatin plus gemcitabine in platinum-refractory ovarian or primary peritoneal cancer: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2006;103:446–50.

    Article  CAS  PubMed  Google Scholar 

  46. Matsumoto K, Katsumata N, Yamanaka Y, Yonemori K, Kohno T, Shimizu C, et al. The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer. Gynecol Oncol. 2006;100:412–6.

    Article  CAS  PubMed  Google Scholar 

  47. Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, et al. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007;25:2811–8.

    Article  CAS  PubMed  Google Scholar 

  48. Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, et al. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008;26:890–6.

    Article  CAS  PubMed  Google Scholar 

  49. Watanabe Y, Koike E, Nakai H, Etoh T, Hoshiai H. Phase II study of single-agent gemcitabine in heavily pretreated Japanese patients with recurrent ovarian cancer. Int J Clin Oncol. 2008;13:345–8.

    Article  CAS  PubMed  Google Scholar 

  50. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19:3312–22.

    Article  CAS  PubMed  Google Scholar 

  51. Kudelka AP, Tresukosol D, Edwards CL, Freedman RS, Levenback C, Chantarawiroj P, et al. Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma. J Clin Oncol. 1996;14:1552–7.

    Article  CAS  PubMed  Google Scholar 

  52. ten Bokkel Huinink W, Lane SR, Ross GA. International Topotecan Study G. 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  PubMed  Google Scholar 

  53. Shimamoto K, Saito T, Nagayama R, Yamaguchi S, Shimada T, Ariyoshi K, et al. Nogitecan hydrochloride treatment for patients with recurrent ovarian cancer. Gan To Kagaku Ryoho. 2015;42:821–5.

    PubMed  Google Scholar 

  54. Katsumata N, Tsunematsu R, Tanaka K, Terashima Y, Ogita S, Hoshiai H, et al. A phase II trial of docetaxel in platinum pre-treated patients with advanced epithelial ovarian cancer: a Japanese cooperative study. Ann Oncol. 2000;11:1531–6.

    Article  CAS  PubMed  Google Scholar 

  55. Gynecologic Oncology G, Markman M, Blessing J, Rubin SC, Connor J, Hanjani P, et al. 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.

    Article  CAS  Google Scholar 

  56. Kita T, Kikuchi Y, Takano M, Suzuki M, Oowada M, Konno R, et al. The effect of single weekly paclitaxel in heavily pretreated patients with recurrent or persistent advanced ovarian cancer. Gynecol Oncol. 2004;92:813–8.

    Article  CAS  PubMed  Google Scholar 

  57. Omura GA, Brady MF, Look KY, Averette HE, Delmore JE, Long HJ, et al. Phase III trial of paclitaxel at two dose levels, the higher dose accompanied by filgrastim at two dose levels in platinum-pretreated epithelial ovarian cancer: an intergroup study. J Clin Oncol. 2003;21:2843–8.

    Article  CAS  PubMed  Google Scholar 

  58. McNeish IA, Ledermann JA, Webber L, James L, Kaye SB, Hall M, et al. A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancerdagger. Ann Oncol. 2014;25:1988–95.

    Article  CAS  PubMed  Google Scholar 

  59. Eckhardt S, Hernadi Z, Thurzo L, Telekes A, Sopkova B, Mechl Z, et al. Phase II clinical evaluation of etoposide (VP-16-213, Vepesid) as a second-line treatment in ovarian cancer. Results of the South-East European Oncology Group (SEEOG) Study. Oncology. 1990;47:289–95.

    Article  CAS  PubMed  Google Scholar 

  60. Hoskins PJ, Swenerton KD. Oral etoposide is active against platinum-resistant epithelial ovarian cancer. J Clin Oncol. 1994;12:60–3.

    Article  CAS  PubMed  Google Scholar 

  61. Alici S, Saip P, Eralp Y, Aydiner A, Topuz E. Oral etoposide (VP16) in platinum-resistant epithelial ovarian cancer (EOC). Am J Clin Oncol. 2003;26:358–62.

    CAS  PubMed  Google Scholar 

  62. Rose PG, Blessing JA, Mayer AR, Homesley HD. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998;16:405–10.

    Article  CAS  PubMed  Google Scholar 

  63. Nishio S, Sugiyama T, Shouji T, Yoshizaki A, Kitagawa R, Ushijima K, et al. Pilot study evaluating the efficacy and toxicity of irinotecan plus oral etoposide for platinum- and taxane-resistant epithelial ovarian cancer. Gynecol Oncol. 2007;106:342–7.

    Article  CAS  PubMed  Google Scholar 

  64. Matsumoto K, Katsumata N, Shibata T, Satoh T, Saitou M, Yunokawa M, et al. Phase II trial of oral etoposide plus intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503). Gynecol Oncol. 2015;136:218–23.

    Article  CAS  PubMed  Google Scholar 

  65. Watanabe Y, Etoh T, Koike E, Mizuno Y, Wang WM, Hoshiai H. Feasibility study of oral cyclophosphamide salvage therapy for the treatment of heavily pretreated patients with recurrent epithelial ovarian cancer. Int J Clin Oncol. 2010;15:468–71.

    Article  CAS  PubMed  Google Scholar 

  66. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med. 2001;7:987–9.

    Article  CAS  PubMed  Google Scholar 

  67. Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004;10:145–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.

    Article  CAS  PubMed  Google Scholar 

  69. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007;25:1539–44.

    Article  CAS  PubMed  Google Scholar 

  70. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542–50.

    Article  CAS  PubMed  Google Scholar 

  71. 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 

  72. Wright JD, Hagemann A, Rader JS, Viviano D, Gibb RK, Norris L, et al. Bevacizumab combination therapy in recurrent, platinum-refractory, epithelial ovarian carcinoma: A retrospective analysis. Cancer. 2006;107:83–9.

    Article  CAS  PubMed  Google Scholar 

  73. Garcia AA, Hirte H, Fleming G, Yang D, Tsao-Wei DD, Roman L, 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. 2008;26:76–82.

    Article  CAS  PubMed  Google Scholar 

  74. Hatake K, Doi T, Uetake H, Takahashi Y, Ishihara Y, Shirao K. Bevacizumab safety in Japanese patients with colorectal cancer. Jpn J Clin Oncol. 2016;46:234–40.

    Article  PubMed  Google Scholar 

  75. Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. Bevacizumab combined with 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 

  76. Husain A, Wang Y, Hanker LC, Ojeda B, Anttila M, Breda E, et al. Independent radiologic review of AURELIA, a phase 3 trial of bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer. Gynecol Oncol. 2016;142:465–70.

    Article  CAS  PubMed  Google Scholar 

  77. Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013;14:29–37.

    Article  CAS  PubMed  Google Scholar 

  78. Takeda M, Yamanaka T, Seto T, Hayashi H, Azuma K, Okada M, et al. Bevacizumab beyond disease progression after first-line treatment with bevacizumab plus chemotherapy in advanced nonsquamous non-small cell lung cancer (West Japan Oncology Group 5910L): An open-label, randomized, phase 2 trial. Cancer. 2016;122:1050–9.

    Article  CAS  PubMed  Google Scholar 

  79. Matulonis UA, Berlin S, Ivy P, Tyburski K, Krasner C, Zarwan C, et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol. 2009;27:5601–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Friedlander M, Hancock KC, Rischin D, Messing MJ, Stringer CA, Matthys GM, et al. A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol. 2010;119:32–7.

    Article  CAS  PubMed  Google Scholar 

  81. Ledermann JA, Embleton AC, Raja F, Perren TJ, Jayson GC, Rustin GJ, et al. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;387:1066–74.

    Article  CAS  PubMed  Google Scholar 

  82. Matsumura N, Mandai M, Okamoto T, Yamaguchi K, Yamamura S, Oura T, et al. Sorafenib efficacy in ovarian clear cell carcinoma revealed by transcriptome profiling. Cancer Sci. 2010;101:2658–63.

    Article  CAS  PubMed  Google Scholar 

  83. Koshiyama M, Matsumura N, Baba T, Yamaguchi K, Yoshioka Y, Konishi I. Two cases of recurrent ovarian clear cell carcinoma treated with sorafenib. Cancer Biol Ther. 2014;15:22–5.

    Article  CAS  PubMed  Google Scholar 

  84. Karlan BY, Oza AM, Richardson GE, Provencher DM, Hansen VL, Buck M, et al. Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients with recurrent ovarian cancer. J Clin Oncol. 2012;30:362–71.

    Article  CAS  PubMed  Google Scholar 

  85. Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, et al. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014;15:799–808.

    Article  CAS  PubMed  Google Scholar 

  86. Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, et al. Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): long-term survival, impact of ascites, and progression-free survival-2. Gynecol Oncol. 2016;143:27–34.

    Article  CAS  PubMed  Google Scholar 

  87. Okazaki T, Chikuma S, Iwai Y, Fagarasan S, Honjo T. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol. 2013;14:1212–8.

    Article  CAS  PubMed  Google Scholar 

  88. Kooi S, Zhang HZ, Patenia R, Edwards CL, Platsoucas CD, Freedman RS. HLA class I expression on human ovarian carcinoma cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro in low concentrations of recombinant interleukin-2. Cell Immunol. 1996;174:116–28.

    Article  CAS  PubMed  Google Scholar 

  89. Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A. 2007;104:3360–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8:467–77.

    Article  CAS  PubMed  Google Scholar 

  91. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.

    Article  CAS  PubMed  Google Scholar 

  92. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30.

    Article  CAS  PubMed  Google Scholar 

  94. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–39.

    Article  CAS  PubMed  Google Scholar 

  95. Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, et al. Safety and antitumor activity of Anti-PD-1 antibody, Nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2015;33:4015–22.

    Article  CAS  PubMed  Google Scholar 

  96. Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A, et al. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A. 2008;105:3005–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  97. Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, et al. Chemotherapy induces programmed cell death-ligand 1 overexpression via the nuclear factor-kappab to foster an immunosuppressive tumor microenvironment in ovarian cancer. Cancer Res. 2015;75:5034–45.

    Article  CAS  PubMed  Google Scholar 

  98. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Hamanishi J, Mandai M, Konishi I. Immune checkpoint inhibition in ovarian cancer. Int Immunol. 2016;28:339–48.

    Article  CAS  PubMed  Google Scholar 

  100. Kunos CA, Sill MW, Buekers TE, Walker JL, Schilder JM, Yamada SD, et al. Low-dose abdominal radiation as a docetaxel chemosensitizer for recurrent epithelial ovarian cancer: a phase I study of the Gynecologic Oncology Group. Gynecol Oncol. 2011;120:224–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Viswanathan AN, Lee H, Berkowitz R, Berlin S, Campos S, Feltmate C, et al. A prospective feasibility study of radiation and concurrent bevacizumab for recurrent endometrial cancer. Gynecol Oncol. 2014;132:55–60.

    Article  CAS  PubMed  Google Scholar 

  102. Yahara K, Ohguri T, Imada H, Yamaguchi S, Kawagoe T, Matsuura Y, et al. Epithelial ovarian cancer: definitive radiotherapy for limited recurrence after complete remission had been achieved with aggressive front-line therapy. J Radiat Res. 2013;54:322–9.

    Article  PubMed  Google Scholar 

  103. Lee SW, Park SM, Kim YM, Kim YS, Choi EK, Kim DY, et al. Radiation therapy is a treatment to be considered for recurrent epithelial ovarian cancer after chemotherapy. Tumori. 2011;97:590–5.

    PubMed  Google Scholar 

  104. Chundury A, Apicelli A, DeWees T, Powell M, Mutch D, Thaker P, et al. Intensity modulated radiation therapy for recurrent ovarian cancer refractory to chemotherapy. Gynecol Oncol. 2016;141:134–9.

    Article  PubMed  Google Scholar 

  105. Machida S, Takei Y, Yoshida C, Takahashi Y, Koyanagi T, Sato N, et al. Radiation therapy for chemotherapy-resistant recurrent epithelial ovarian cancer. Oncology. 2014;86:232–8.

    Article  CAS  PubMed  Google Scholar 

  106. Fujiwara K, Suzuki S, Yoden E, Ishikawa H, Imajo Y, Kohno I. Local radiation therapy for localized relapsed or refractory ovarian cancer patients with or without symptoms after chemotherapy. Int J Gynecol Cancer. 2002;12:250–6.

    Article  CAS  PubMed  Google Scholar 

  107. Lee YK, Park NH, Kim JW, Song YS, Kang SB, Lee HP. Gamma-knife radiosurgery as an optimal treatment modality for brain metastases from epithelial ovarian cancer. Gynecol Oncol. 2008;108:505–9.

    Article  PubMed  Google Scholar 

  108. Ratner ES, Toy E, O'Malley DM, McAlpine J, Rutherford TJ, Azodi M, et al. Brain metastases in epithelial ovarian and primary peritoneal carcinoma. Int J Gynecol Cancer. 2009;19:856–9.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroaki Kobayashi M.D., Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Yanazume, S., Kobayashi, H. (2017). Treatment of Recurrent 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_14

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-4160-0_14

  • 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