Taiwanese Journal of Obstetrics and Gynecology
Volume 46, Issue 4 , Pages 379-388, December 2007

Management of Relapsed/Refractory Epithelial Ovarian Cancer: Current Standards and Novel Approaches

  • Hao Lin
  • ,
  • Chan-Chao Changchien

      Affiliations

    • Corresponding Author InformationCorrespondence to: Dr Chan-Chao Changchien, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital–Kaohsiung Medical Center, 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Taiwan

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

Accepted 14 June 2007.

Article Outline

SUMMARY 

Approximately 60% to 70% of epithelial ovarian cancers are diagnosed at an advanced stage. Treatment of advanced disease involves cytoreductive surgery followed by systemic treatment with paclitaxel and platinum. Overall response rates are high, ranging from 70–80%; however, 70–80% of responders will relapse and require further systemic chemotherapy. Patients who experience disease relapse with platinum-free interval of less than 6 months are considered as platinum-refractory/resistant individuals. In this clinical setting, agents with non-cross-resistance to first-line therapy and favorable toxicity profiles are usually chosen. In the management of relapsed patients with platinum-free interval over 6 months, the generally accepted recommendation is retreatment with a platinum plus paclitaxel combination. In general, treatment of recurrent disease is palliative and is initiated with the goals of controlling disease-related symptoms, limiting treatment-related toxicity, maintaining or improving quality of life, delaying time to progression, and prolonging survival. A number of currently available and novel investigating agents in recurrent epithelial ovarian cancer will be reviewed in this context.

Key Word:  relapsed ovarian cancer

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References 

  1. Female genital tract malignancy. Taiwan Cancer Registry, Bureau of Health Promotion, Department of Health, Republic of China, 2007. Available at: http://crs.cph.ntu.edu.tw/crs_c/annual.html
  2. du Bois A , Lück HJ , Meier W , et al.   A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer . J Natl Cancer Inst . 2003;95:1320–1329
  3. Markman M , Hoskins W . Responses to salvage chemotherapy in ovarian cancer: A critical need for precise definitions of the treated population . J Clin Oncol . 1992;10:513–514
  4. Niloff JM , Knapp RC , Lavin PT , et al.   The CA 125 assay as a predictor of clinical recurrence in epithelial ovarian cancer . Am J Obstet Gynecol . 1986;155:56–60
  5. Vergote IB , Abeler VM , Bormer OP , Stigbrand T , Trope C , Nustad K . CA125 and placental alkaline phosphatase as serum tumor markers in epithelial ovarian carcinoma . Tumour Biol . 1992;13:168–174
  6. Muggia FM , Hainsworth JD , Jeffers S , et al.   Phase II study of liposomal doxorubicin in refractory ovarian cancer: anti-tumor activity and toxicity modification by liposomal encapsulation . J Clin Oncol . 1997;15:987–993
  7. Gordon AN , Granai CO , Rose PG , et al.   Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer . J Clin Oncol . 2000;18:3093–3100
  8. Chou HH , Wang KL , Chen CA , et al.   Pegylated liposomal doxorubicin (Lipo-Dox) for platinum-resistant or refractory epithelial ovarian carcinoma: a Taiwanese gynecologic oncology group study with long-term follow-up . Gynecol Oncol . 2006;101:423–428
  9. Lin H , Tseng CW , Chang HY , Lu HM , Ou YC , Changchien CC . Evaluation of pegylated liposomal doxorubicin in the treatment of both platinum- and paclitaxel-refractory epithelial ovarian cancer . Taiwan J Obstet Gynecol . 2004;43:140–143
  10. Kudelka AP , Tresukosol D , Edwards CL , et al.   Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma . J Clin Oncol . 1996;14:1552–1557
  11. Creemers GJ , Bolis G , Gore M , et al.   Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study . J Clin Oncol . 1996;14:3056–3061
  12. Bookman MA, Malmström H, Bolis G, Gordon A, Lissoni A, Krebs JB, et al. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel . J Clin Oncol . 1998;16:3345–3352
  13. Gordon AN , Fleagle JT , Guthrie D , Parkin DE , Gore ME , Lacave AJ . Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxoru-bicin versus topotecan . J Clin Oncol . 2001;19:3312–3322
  14. Safra T , Menczer J , Bernstein R , et al.   Efficacy and toxicity of weekly topotecan in recurrent epithelial ovarian and primary peritoneal cancer . Gynecol Oncol . 2007;105:205–210
  15. Spannuth WA , Leath CA , Huh WK , et al.   A phase II trial of weekly topotecan for patients with secondary platinum-resistant recurrent epithelial ovarian carcinoma following the failure of second-line therapy . Gynecol Oncol . 2007;104:591–595
  16. Fennelly D , Aghajanian C , Shapiro F , et al.   Phase I and phar-macologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer . J Clin Oncol . 1997;15:187–192
  17. Abu-Rustum N , Aghajanian C , Barakat RR , Fennelly D , Shapiro F , Spriggs D . Salvage weekly paclitaxel in recurrent ovarian cancer . Semin Oncol . 1997;24(5 Suppl 15):S62–S67
  18. Andersson H , Horvath G , Mellqvist L , Westberg R . Taxol given weekly in advanced previously treated ovarian carcinomas: a pilot study . Int J Gynecol Cancer . 1997;7:262–266
  19. Markman M, Hall J, Spitz D, Weiner S, Carson L, Van Le L, et al. Phase II trial of weekly single-agent paclitaxel in platinum/paclitaxel-refractory ovarian cancer . J Clin Oncol . 2002;20:2365–2369
  20. Kita T , Kikuchi Y , Takano M , et al.   The effect of single weekly paclitaxel in heavily pretreated patients with recurrent or persistent advanced ovarian cancer . Gynecol Oncol . 2004;92:813–818
  21. 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;101:436–440
  22. Le T , Hopkins L , Baines KA , Rambout L , Al Hayki M , Kee Fung MF . Prospective evaluations of continuous weekly paclitaxel regimen in recurrent platinum-resistant epithelial ovarian cancer . Gynecol Oncol . 2006;102:49–53
  23. Hoskins PJ , Swenerton KD . Oral etoposide is active against platinum-resistant epithelial ovarian cancer . J Clin Oncol . 1994;12:60–63
  24. 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;16:405–410
  25. Lund B , Hansen OP , Theilade K , Hansen M , Neijt JP . Phase II study of gemcitabine (2′, 2′-difluorodeoxycytidine) in previously treated ovarian cancer patients . J Natl Cancer Inst . 1994;86:1530–1533
  26. Shapiro JD, Millward MJ, Rischin D, Michael M, Walcher V, Francis PA, et al. Activity of gemcitabine in patients with advanced ovarian cancer: responses seen following platinum and paclitaxel . Gynecol Oncol . 1996;63:89–93
  27. D'Agostino G , Amant F , Berteloot P , Scambia G , Vergote I . Phase II study of gemcitabine in recurrent platinum-and paclitaxel-resistant ovarian cancer . Gynecol Oncol . 2003;88:266–269
  28. Markman M , Webster K , Zanotti K , Kulp B , Peterson G , Belinson J . Phase 2 trial of single-agent gemcitabine in platinum-paclitaxel refractory ovarian cancer . Gynecol Oncol . 2003;90:593–596
  29. Rose PG, Blessing JA, Ball HG, Hoffman J, Warshal D, DeGeest K, et al. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study . Gynecol Oncol . 2003;88:130–135
  30. 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;91:573–576
  31. Berkenblit A , Seiden MV , Matulonis UA , et al.   A phase II trial of weekly docetaxel in patients with platinum-resistant epithelial ovarian, primary peritoneal serous cancer, or fallopian tube cancer . Gynecol Oncol . 2004;95:624–631
  32. Tinker AV , Gebski V , Fitzharris B , et al.   Phase II trial of weekly docetaxel for patients with relapsed ovarian cancer who have previously received paclitaxel—ANZGOG 02-01 . Gynecol Oncol . 2007;104:647–653
  33. Burger RA , Sill M , Monk BJ , Greer B , 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(Suppl):5009; 16 [Abstract]
  34. Cannistra SA , Matulonis U , Penson R , et al.   Bevacizumab in patients with advanced platinum-resistant ovarian cancer . J Clin Oncol . 2006;24(18 Suppl):5006; [Abstract]
  35. Han ES , Monk BJ . What is the risk of bowel perforation associated with bevacizumab therapy in ovarian cancer? . Gynecol Oncol . 2007;105:3–6
  36. Taamma A , Misset JL , Riofrio M , et al.   Phase I and pharma-cokinetic study of ecteinascidin-743, a new marine compound, administered as a 24-hour continuous infusion in patients with solid tumors . J Clin Oncol . 2001;19:1256–1265
  37. Ryan DP , Supko JG , Eder JP , et al.   Phase I and pharmacoki-netic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies . Clin Cancer Res . 2001;7:231–242
  38. Twelves C , Hoekman K , Bowman A , et al.   Phase I and phar-macokinetic study of Yondelis (Ecteinascidin-743; ET-743) administered as an infusion over 1 h or 3 h every 21 days in patients with solid tumours . Eur J Cancer . 2003;39:1842–1851
  39. Sessa C , De Braud F , Perotti A , et al.   Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails . J Clin Oncol . 2005;23:1867–1874
  40. Altmann KH , Wartmann M , O'Reilly T . Epothilones and related structures: a new class of microtubule inhibitors with potent in vivo antitumor activity . Biochim Biophys Acta . 2000;1470:M79–M91
  41. Chou TC , Zhang XG , Harris CR , et al.   Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel . Proc Natl Acad Sci USA . 1998;95:15798–15802
  42. Kowalski RJ , Giannakakou P , Hamel E . Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol(r)) . J Biol Chem . 1997;272:2534–2541
  43. Smit WM , Sufliarsky J , Spanik S , et al.   Phase I/II dose-escalation trial of patupilone every 3 weeks in patients with relapsed/refractory ovarian cancer . J Clin Oncol . 2005;23(16 Suppl):5056; [Abstract]
  44. Patupilone versus doxorubicin in patients with ovarian, primary fallopian, or peritoneal cancer . Available at: http://www.clinicaltrials.gov/ct/show/NCT00262990?order=7
  45. Rosario LA , O'Brien ML , Henderson CJ , Wolf CR , Tew KD . Cellular response to a glutathione S-transferase P1-1 activated prodrug . Mol Pharmacol . 2000;58:167–174
  46. Townsend DM , Shen H , Staros AL , Gate L , Tew KD . Efficacy of a glutathione S-transferase pi-activated prodrug in platinum-resistant ovarian cancer cells . Mol Cancer Ther . 2002;1:1089–1095
  47. Kavanagh JJ , Gershenson DM , Choi H , et al.   Multi-institutional phase 2 study of TLK286 (TELCYTA, a glu-tathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer . Int J Gynecol Cancer . 2005;15:593–600
  48. Kavanagh J , Lewis L , Choi R , et al.   Phase 1–2a study of TLK286 (a novel glutathione analog) in combination with carboplatin in platinum refractory or resistant (= 3rd line) ovarian cancer . J Clin Oncol . 2004;22(14 Suppl):5060; [Abstract]
  49. Brown GL , Lewis L , Choi H , et al.   Phase 1–2a dose ranging study of TLK286 (a novel glutathione analog) in combination with liposomal doxorubicin in platinum refractory or resistant ovarian cancer . J Clin Oncol . 2004;22(14 Suppl):5062; [Abstract]
  50. Ovarian cancer clinical trials . Available at: http://www.assist-ovarian.com/
  51. Alvero AB , O'Malley D , Brown D , et al.   Molecular mechanism of phenoxodiol-induced apoptosis in ovarian carcinoma cells . Cancer . 2006;106:599–608
  52. Sapi E , Alvero AB , Chen W , et al.   Resistance of ovarian carcinoma cells to docetaxel is XIAP dependent and reversible by phenoxodiol . Oncol Res . 2004;14:567–578
  53. Kluger HM , McCarthy MM , Alvero AB , et al.   The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by phenoxodiol is associated with carboplatin sensitization . J Transl Med . 2007;5:6
  54. Choueiri TK , Mekhail T , Hutson TE , Ganapathi R , Kelly GE , Bukowski RM . Phase I trial of phenoxodiol delivered by continuous intravenous infusion in patients with solid cancer . Ann Oncol . 2006;17:860–865
  55. OVATURE (OVArian TUmor REsponse) Study: a phase III study of weekly carboplatin with and without phenoxodiol in patients with platinum-resistant, recurrent epithelial ovarian cancer . Available at: http://clinicaltrials.gov/ct/show/NCT00382811
  56. Berek JS , Bertelsen K , du Bois A , et al.   Advanced epithelial ovarian cancer: 1998 consensus statements . Ann Oncol . 1999;10(Suppl 1):S87–S92
  57. Salani R, Santillan A, Zahurak ML, Giuntoli RL, Gardner GJ, Armstrong DK, et al. Secondary cytore-ductive surgery for localized, recurrent epithelial ovarian cancer: analysis of prognostic factors and survival outcome . Cancer . 2007;109:685–691
  58. Harter P , Bois A , Hahmann M , et al.   Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Committee; AGO Ovarian Cancer Study Group. Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial . Ann Surg Oncol . 2006;13:1702–1710
  59. Parmar MK , Ledermann JA , Colombo N , 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;361:2099–2106
  60. Pfisterer J , Plante M , Vergote I , et al.   Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer . J Clin Oncol . 2006;24:4699–4707
  61. Ferrero JM , Weber B , Geay JF , et al.   Second-line chemotherapy with pegylated liposomal doxorubicin and carboplatin is highly effective in patients with advanced ovarian cancer in late relapse: a GINECO phase II trial . Ann Oncol . 2007;18:263–268
  62. 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;22:3120–3125
  63. Cohen RB , Schilder RJ , Cheng J , et al.   Final results of a combination study between trabectedin and pegylated liposomal doxorubicin (PLD) in patients with advanced malignancies . J Clin Oncol . 2005;23(16 Suppl):3074; [Abstract]

PII: S1028-4559(08)60007-8

doi:10.1016/S1028-4559(08)60007-8

Taiwanese Journal of Obstetrics and Gynecology
Volume 46, Issue 4 , Pages 379-388, December 2007