Current Oncology Reports

, Volume 13, Issue 6, pp 459–471 | Cite as

Recurrent Ovarian Cancer: When and How to Treat

Gynecologic Cancers (Jonathan A. Ledermann, Section Editor)


Notwithstanding continuing efforts to improve the primary treatment for ovarian cancer, most patients will ultimately develop recurrent disease. The benefits of detection and early systemic treatment of recurrence are now in doubt following the presentation of the MRC/EORTC CA125 surveillance trial. The impact of secondary cytoreductive surgery on survival requires more investigation. The role of antiangiogenic and other biological agents such as PARP inhibitors is becoming increasingly important for patients as an addition or alternative to the more conventional cytotoxic therapies available. Uncertainties and choices abound both in the treatment of recurrent ovarian cancer and the timing of such interventions. This article not only explores how to treat these patients but also the controversial issue of when to treat. Educating and involving the patient in decisions about their treatment options is of paramount importance.


Ovarian carcinoma CA125 Surgery Radiotherapy Follow up Platinum-free intervals Platinum hypersensitivity Chemotherapy Antiangiogenesis PARP inhibitors Hormones Tyrosine kinase inhibitors 



M. Hall: consultant to and honoraria from Roche; G. Rustin: board membership for Roche, Oxigene, and AstraZeneca, and honoraria from Boehringer-Ingelheim.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Menczer J, Chetrit A, Sadetzki S, et al. Follow-up of ovarian and primary peritoneal carcinoma: the value of physical examination in patients with pretreatment elevated CA125 levels. Gynecol Oncol. 2006;103:137–40.PubMedCrossRefGoogle Scholar
  2. 2.
    Chan KK, Tam KF, Tse KY, Ngan HY. The role of regular physical examination in the detection of ovarian cancer recurrence. Gynaecol Oncol. 2008;110:158–61.CrossRefGoogle Scholar
  3. 3.
    Bradley EJ, Pitts MK, Redman CWE, Calvert E. The experience of long-term hospital follow-up for women who have suffered early stage gynecological cancer: a qualitative interview study. Int J Gynecol Oncol. 1999;9:491–6.CrossRefGoogle Scholar
  4. 4.
    Rustin GJ, Nelstrop AE, Tuxen MK, Lambert HE. Defining progression of ovarian carcinoma during follow-up according to CA 125: a North Thames Ovary Group Study. Ann Oncol. 1996;7:361–4.PubMedGoogle Scholar
  5. 5.
    Rustin GJS, Marples M, Nelstrop AE, et al. Use of CA 125 to define progression of ovarian cancer in patients with persistently elevated levels. J Clin Oncol. 2001;19:4054–7.PubMedGoogle Scholar
  6. 6.
    Prat A, Parera M, Adamo B, et al. Risk of recurrence during follow-up for optimally treated advanced epithelial ovarian cancer (EOC) with a low-level increae of serum CA-125 levels. Ann Oncol. 2009;120:294–7.Google Scholar
  7. 7.
    Wilder JL, Pavlik E, Straughn JM, et al. Clinical implications of a rising serum CA-125 within the normal range in patients with epithelial ovarian cancer: a preliminary investigation. Gynecol Oncol. 2003;89:233–5.PubMedCrossRefGoogle Scholar
  8. 8.
    • Rustin GJ, van der Burg ME, Griffin CL, et al. Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet. 2010;376:1155–63. Seminal trial proving that treating patients with ROC on the basis of their rising CA-125 does NOT alter their overall survival and reduces quality of life. PubMedCrossRefGoogle Scholar
  9. 9.
    Gadducci A, Fuso L, Cosio S, et al. Are surveillance procedures of clinical benefit for patients treated for ovarian cancer? a retrospective Italian multicentric study. Int J Gynecol Canc. 2009;19:367–74.CrossRefGoogle Scholar
  10. 10.
    Tanner EJ, Chi DS, Eisenhauer EL, et al. Surveillance for the detection of recurrent ovarian cancer: survival impact or lead-time bias? Gynecol Oncol. 2010;117:336–40.PubMedCrossRefGoogle Scholar
  11. 11.
    Gadducci A, Cosio S. Surveillance of patients after initial treatment of ovarian cancer. Crit Rev Oncol Hematol. 2009;71:43–52.PubMedCrossRefGoogle Scholar
  12. 12.
    Coakley FV, Choi PH, Gougoutas CA, et al. Peritoneal metastases: detection with spiral CT in patients with ovarian cancer. Radiology. 2002;223:495–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Thrall MM, DeLoia JA, Gallion H, Avril N. Clinical use of combined positron emission tomography and computed tomography (FDG-PET/CT) in recurrent ovarian cancer. Gynecol Oncol. 2007;105:17–22.PubMedCrossRefGoogle Scholar
  14. 14.
    Fulham MJ, Carter J, Baldey A, et al. The impact of PET-CT in suspected recurrent ovarian cancer: a prospective multi-centre study as part of the Australian PET Data Collection Project. Gynecol Oncol. 2009;112:462–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Cannistra SA. Evaluating new regimens in recurrent ovarian cancer: how much evidence is good enough? J Clin Oncol. 2010;28:3101–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Parmar MKB, 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;361:2099–106.PubMedCrossRefGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    Issaeva N, Thomas HD, Djureinovic T, et al. 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance. Canc Res. 2010;70:6268–76.CrossRefGoogle Scholar
  19. 19.
    Friedlander M, Butow P, Stockler M, et al. Symptom control in patients with recurrent ovarian cancer: measuring the benefit of palliative chemotherapy in women with platinum refractory/resistant ovarian cancer. Int J Gynaecol Canc. 2009;19 Suppl 2:S44–8.CrossRefGoogle Scholar
  20. 20.
    Gadducci A, Iacconi P, Cosio S, et al. Complete salvage surgical cytoreduction improves further survival of patients with late recurrent ovarian cancer. Gynecol Oncol. 2000;79:344–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Bristow RE, Puri I, Chi DS. Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol. 2009;112:265–74.PubMedCrossRefGoogle Scholar
  22. 22.
    Oksefjell H, Sandstad B, Tropé C. The role of secondary cytoreduction in the management of the first relapse in epithelial ovarian cancer. Ann Oncol. 2009;20:286–93.PubMedCrossRefGoogle Scholar
  23. 23.
    Eisenkop SM, Friedman RL, Spirtos NM. The role of secondary cytoreductive surgery in the treatment of patients with recurrent epithelial ovarian carcinoma. Cancer. 2000;88:144–53.PubMedCrossRefGoogle Scholar
  24. 24.
    Scarabelli C, Gallo A, Carbone A. Secondary cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma. Gynecol Oncol. 2001;83:504–12.PubMedCrossRefGoogle Scholar
  25. 25.
    Tebes SJ, Sayer RA, Palmer JM, et al. Cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma. Gynecol Oncol. 2007;106:482–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Shih KK, Chi DS, Barakat RR, Leitao Jr MM. Tertiary cytoreduction in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer: an updated series. Gynecol Oncol. 2010;117:330–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Harter P, du Bois A, Hahmann M, Hasenburg A, Burges A, Loibl S, et al. Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial. Ann Surg Oncol. 2006;13:1702–10.PubMedCrossRefGoogle Scholar
  28. 28.
    • Harter P, Hahmann M, Lueck HJ, et al. Surgery for recurrent ovarian cancer: role of peritoneal carcinomatosis: exploratory analysis of the DESKTOP I trial about risk factors, surgical implications, and prognostic value of peritoneal carcinomatosis. Ann Surg Oncol. 2009;16:1324–30. Really important piece of work ongoing to elucidate efficacy of surgery in ROC. PubMedCrossRefGoogle Scholar
  29. 29.
    Gelblum D, Mychalczak B, Almadrones L, et al. Palliative benefit of external-beam radiation in the management of platinum refractory epithelial ovarian carcinoma. Gynecol Oncol. 1998;69:36–41.PubMedCrossRefGoogle Scholar
  30. 30.
    Firat S, Erickson B. Selective irradiation for the treatment of recurrent ovarian carcinoma involving the vagina or rectum. Gynecol Oncol. 2001;80:213–20.PubMedCrossRefGoogle Scholar
  31. 31.
    Choan E, Quon M, Gallant V, Samany R. Effective palliative radiotherapy for symptomatic recurrent or residual ovarian cancer. Gynecol Oncol. 2006;102:204–9.CrossRefGoogle Scholar
  32. 32.
    De Meerleer G, Vandecasteele K, Ost P, et al. Whole abdominopelvic radiotherapy using intensity-modulated arc therapy in the palliative treatment of chemotherapy-resistant ovarian cancer with bulky peritoneal disease: a single-institution experience. Int J Radiat Oncol Biol Phys. 2011;79:775–81.PubMedCrossRefGoogle Scholar
  33. 33.
    Hall M, Ulahannan D, Shreeves G, et al. How much benefit is obtained from therapy for relapsed ovarian cancer (ROC)? impact of initial stage, age and medical advances. ESGO. 2011:Abstract 101.Google Scholar
  34. 34.
    Blackledge G, Lawton F, Redman C, Kelly K. Response of patients in phase II studies of chemotherapy in ovarian cancer: implications for patient treatment and the design of phase II trials. Br J Canc. 1989;59:650–3.CrossRefGoogle Scholar
  35. 35.
    Markman M, Markman J, Webster K, 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.PubMedCrossRefGoogle Scholar
  36. 36.
    Pujade-Lauraine E, Paraiso D, Cure H, et al. Predicting the effectiveness of chemotherapy (CX) in patients with recurrent ovarian cancer (ROC): a GINECO study (abstract 829). Proc Am Soc Clin Oncol. 2002;208a:21.Google Scholar
  37. 37.
    Tanguay JS, Ansari J, Buckley L, Fernando I. Epithelial ovarian cancer: role of pegylated liposomal doxorubicin in prolonging the platinum-free interval and cancer antigen 125 trends during treatment. Int J Gynecol Oncol. 2009;19:361–6.CrossRefGoogle Scholar
  38. 38.
    Colombo N. Efficacy of trabectidin in platinum-sensitive relapsed ovarian cancer: new data from the randomised OVA-301 study. Int J Gynecol Oncol. 2011;21:S12–6.CrossRefGoogle Scholar
  39. 39.
    Kavanagh J, Tresukosol D, Edwards C, et al. Carboplatin reinduction after taxane in patients with platinum-refractory epithelial ovarian cancer. J Clin Oncol. 1995;13:1584–8.PubMedGoogle Scholar
  40. 40.
    Bryant CS, Kumar S, Spannuth W, et al. Feasibility of extension of platinum-free interval with weekly bolus topotecan and subsequent platinum retreatment outcomes in recurrent ovarian cancer. Arch Gynecol Obstet. 2011;283:361–7.PubMedCrossRefGoogle Scholar
  41. 41.
    See HT, Freedman RS, Kudelka AP, et al. Retrospective review: retreatment of patients with ovarian cancer with carboplatin after platinum resistance. Int J Gynecol Canc. 2005;15:209–16.CrossRefGoogle Scholar
  42. 42.
    Monk BJ, Herzog TJ, Kaye S, et al. Trabectedin plus pegylated liposomal doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010;28:3107–14.PubMedCrossRefGoogle Scholar
  43. 43.
    Poveda A, Vergote I, Tjulandin 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.PubMedGoogle Scholar
  44. 44.
    Vergote I, Finkler N, Hall J, et al. Randomized phase III study of canfosfamide in combination with Pegylated Liposomal Doxorubicin (PLD) as compared to PLD alone in platinum resistant ovarian cancer. Int J Gynecol Canc. 2010;20(5):772–80.CrossRefGoogle Scholar
  45. 45.
    Sharma R, Graham J, Mitchell H, et al. Extended weekly dose-dense paclitaxel/carboplatin is feasible and active in heavily pre-treated platinum-resistant recurrent ovarian cancer. Br J Canc. 2010;100:707–12.CrossRefGoogle Scholar
  46. 46.
    Baird RD, Tan DS, Kaye SB. Weekly paclitaxel in the treatment of recurrent ovarian cancer. Nat Rev Clin Oncol. 2010;7:575–82.PubMedCrossRefGoogle Scholar
  47. 47.
    Rose PG, Monk BJ, Provencher D, et al. An open-label, single-arm phase II study of intravenous weekly (days 1 and 8) topotecan in combination with carboplatin (day 1) every 21 days as second-line therapy in patients with platinum-sensitive relapsed ovarian cancer. Gynecol Oncol. 2011;120:38–42.PubMedCrossRefGoogle Scholar
  48. 48.
    Syrigou E, Makriilia N, Koti I, et al. Hypersensitivity reactions to antineoplastic agents: an overview. Anti Canc Drug. 2009;20:1–6.CrossRefGoogle Scholar
  49. 49.
    Markman M, Moon J, Wilczynski S, et al. Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin in recurrent ovarian cancer: final survival results of a SWOG (S0200) phase 3 randomized trial. Gynecol Oncol. 2010;116:323–5.PubMedCrossRefGoogle Scholar
  50. 50.
    Joly F, Ray-Coquard I, Fabbro M, et al. Decreased hypersensitivity reactions with carboplatin-pegylated liposomal doxorubicin compared to carboplatin-paclitaxel combination: analysis from the GCIG CALYPSO relapsing ovarian cancer trial. Gynecol Oncol. 2011;122:226–32.PubMedCrossRefGoogle Scholar
  51. 51.
    Lee CW, Matulonis UA, Castells MC. Rapid inpatient/outpatient desensitization for chemotherapy hypersensitivity: standard protocol effective in 57 patients for 255 courses. Gynecol Oncol. 2005;99:393–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Williams CJ, Simera I, Bryant A. Tamoxifen for relapse of ovarian cancer (review) Cochrane Database. 2010.Google Scholar
  53. 53.
    Thomas SG, Judson P, Carson L, et al. Phase II trial of fulvestrant in the treatment of recurrent ovarian carcinoma. Gynecol Oncol. 2008;111:373–86.CrossRefGoogle Scholar
  54. 54.
    Krasner C. Review of aromatase inhibitors in gynecologic cancers. J Steroid Biochem Mol Biol. 2007;106:76–80.PubMedCrossRefGoogle Scholar
  55. 55.
    Eeles RA, Tan S, Wiltshaw E, et al. Hormone replacement therapy and survival after surgery for ovarian cancer. BMJ. 1991;302:259–62.PubMedCrossRefGoogle Scholar
  56. 56.
    Paskeviciute L, Roed H, Engelholm S. No rules without exception: long-term complete remission observed in a study using a LH-RH agonist in platinum-refractory ovarian cancer. Gynecol Oncol. 2001;86:297–301.CrossRefGoogle Scholar
  57. 57.
    Kumaran G, Jayson G, Clamp A. Antiangiogenic drugs in ovarian cancer. Br J Canc. 2009;100:1–7.CrossRefGoogle Scholar
  58. 58.
    Burger R, Sill M, Monk B, et al. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a gynecologic oncology group study. J Clin Oncol. 2007;25:5165–71.PubMedCrossRefGoogle Scholar
  59. 59.
    Cannistra S, Matulonis U, Penson R, et al. Phase II study of bevacizumab in patients with platinum- resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol;25:5180–6.Google Scholar
  60. 60.
    Han E, Monk B. What is the risk of bowel perforation associated with bevacizumab therapy in ovarian cancer? Gynecol Oncol. 2007;105:3–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Wright D, Secord A, Numnum T, et al. A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer. Int J Gynecol Oncol. 2008;18(3):400–6.CrossRefGoogle Scholar
  62. 62.
    Cheng X, Moroney J, Levenback C, et al. What is the benefit of bevacizumab combined with chemotherapy in patients with recurrent ovarian, fallopian tube or primary peritoneal malignancies? J Chemother. 2009;21(5):566–72.PubMedGoogle Scholar
  63. 63.
    Matei D, Sill MW, DeGeest K, et al. Phase II trial of sorafenib in persistent or recurrent epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC): a gynecologic oncology group (GOG) study. J Clin Oncol. 2008;26:Abstract 5537.Google Scholar
  64. 64.
    Biagi J, Oza A, Chalchal H, et al. A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC clinical trials group study. Ann Oncol. 2010. Epub ahead of print.Google Scholar
  65. 65.
    Ledermann J, Rustin G, Hackshaw A, et al. A randomized phase II placebo-controlled trial using maintenance therapy to evaluate the vascular targeting agent BIBF 1120 following treatment of relapsed ovarian cancer. J Clin Oncol. 2009;27:15s. suppl; abstr 5501.CrossRefGoogle Scholar
  66. 66.
    Friedlander M, Benigno K, Rischin B, et al. Pazopanib (GW786034) is active in women with advanced epithelial ovarian, fallopian tube and peritoneal cancers: results of a phase 2 study. Ann Oncol. 2008;19:211. 6 abstr 6630.Google Scholar
  67. 67.
    • Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 2004;4:423–36. Excellent review of metronomic theory. CrossRefGoogle Scholar
  68. 68.
    Slevin ML, Clark PI, Joel SP, et al. A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer. J Clin Oncol. 1989;7:1333–40.PubMedGoogle Scholar
  69. 69.
    Colleoni M, Rocca A, Sandri T, et al. Low dose oral methotrexate and cyclophosphamide in meta- static breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels. Ann Oncol. 2000;13:73–80.CrossRefGoogle Scholar
  70. 70.
    • Aghajanian C, Finkler NJ, Rutherford T, Smith DA, Yi J, Parmar H, Nycum LR, Sovak MA. OCEANS: a randomised, double-blinded, 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. 2011;ASCO. Good evidence of efficacy of bevacizumab (VEGF inhibition) in ROC. Google Scholar
  71. 71.
    Chura JC, Van Iseghem K, Downs LS Jr, et al. Bevacizumab plus cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Gynaecol Oncol. 2007:326–30.Google Scholar
  72. 72.
    Garcia AA, Hirte H, Fleming G, 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.PubMedCrossRefGoogle Scholar
  73. 73.
    Hall M, GJS. R. A retrospective review of low dose oral cyclophosphamide alone and in combination with tamoxifen and prophylactic warfarin in heavily pretreated ovarian cancer. IJGC. 2010.Google Scholar
  74. 74.
    Chung VM, Ruel C, Cristea M, et al. Randomised pilot trial of oral cyclophosphamide versus oral cyclophosphamide with celecoxib for recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer preliminary data. J Clin Oncol. 2008;26:abstr 16555.Google Scholar
  75. 75.
    Azad N, Posadas E, Kwitkowski V, et al. Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol. 2008;26:3709–14.PubMedCrossRefGoogle Scholar
  76. 76.
    Naumann R, Symanowski J, Ghamande S. PRECEDENT: a randomized phase II trial comparing EC145 and pegylated liposomal doxorubicin (PLD) in combination, versus PLD alone, in subjects with platinum-resistant ovarian cancer. J Clin Oncol. 2010;28:18s. suppl; abstr LBA5012b.Google Scholar
  77. 77.
    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 Canc Res. 2005;11:5539–48.CrossRefGoogle Scholar
  78. 78.
    Gottipati P, Vischioni B, Schultz N, et al. Poly(ADP-Ribose) polymerase is hyperactivated in homologous recombination-defective cells. Canc Res. 2010;70:5389–98.CrossRefGoogle Scholar
  79. 79.
    Turner N, Tutt A, Ashworth A. Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev Canc. 2004;4:814–9.CrossRefGoogle Scholar
  80. 80.
    Gelmon KA, Hirte HW, Robidoux A, et al. Can we define tumors that will respond to PARP inhibitors? a phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer. J Clin Oncol. 2010;28:Abstract:3002.Google Scholar
  81. 81.
    • Audeh MW, Carmichael J, Penson RT, 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. Very exciting new group of agents for ROC. PubMedCrossRefGoogle Scholar
  82. 82.
    • Ledermann JA, Harter P, Gourley C, et al. Phase II randomised placebo controlled study of olaparib (AZD2281) in patients with platinum-sensitivie relapsed serous ovarian cancer. J Clin Oncol. 2011. Equally important initial trial showing that PARPi therapy is applicable to ROC patients without BRCA germline mutations. Google Scholar
  83. 83.
    Fong PC, Yap TA, Boss DS, 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.PubMedCrossRefGoogle Scholar
  84. 84.
    Banerjee S, Kaye SB, Ashworth A. Medscape. Making the best of PARP inhibitors in ovarian cancer. Nat Rev Clin Oncol. 2010;7:508–19.PubMedCrossRefGoogle Scholar
  85. 85.
    Gonzalez-Martinez AJ, Calvo E, Bover I, 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.CrossRefGoogle Scholar
  86. 86.
    Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, 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.PubMedCrossRefGoogle Scholar
  87. 87.
    Strauss HG, Henze A, Teichmann A, et al. Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Gynecol Oncol. 2007;104:612–6.PubMedCrossRefGoogle Scholar
  88. 88.
    Koensgen D, Stengel D, Belau A, et al. Topotecan and carboplatin in patients with platinum-sensitive recurrent ovarian cancer. Results of a multicenter NOGGO: phase I/II study. Canc Chemother Pharmacol. 2008;62:393–400.CrossRefGoogle Scholar
  89. 89.
    Burg ME, van der Gaast A, Vergote I, et al. What is the role of dose-dense therapy? Int J Gynecol Oncol. 2005;15:233–40.CrossRefGoogle Scholar
  90. 90.
    Matulonis UA, Horowitz NS, Campos SM, et al. Phase II study of carboplatin and pemetrexed for the treatment of platinum-sensitive recurrent ovarian cancer. J Clin Oncol. 2008;26:5761–6.PubMedCrossRefGoogle Scholar
  91. 91.
    Sehouli J, Stengel D, Oskay-Oezcelik G, et al. Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the north-eastern german society of gynecological oncology ovarian cancer study group. J Clin Oncol. 2008;26:3176–82.PubMedCrossRefGoogle Scholar
  92. 92.
    Mirza MR, Lund B, Lindegaard JC, et al. A phase II study of combination chemotherapy in early relapsed epithelial ovarian cancer using gemcitabine and pegylated liposomal doxorubicin. Gynecol Oncol. 2010;119:26–31.PubMedCrossRefGoogle Scholar
  93. 93.
    Zanotti KM, Belinson JL, Kennedy AW, et al. Treatment of relapsed carcinoma of the ovary with single-agent paclitaxel following exposure to paclitaxel and platinum employed as initial therapy. Gynecol Oncol. 2000;79:211–5.PubMedCrossRefGoogle Scholar
  94. 94.
    Gordon AN, Fleagle JT, Guthrie D, et al. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19:3312–22.PubMedGoogle Scholar
  95. 95.
    Sehouli J, Stengel D, Harter P, et al. Topotecan weekly versus conventional 5-day schedule in patients with platinum-resistant ovarian cancer: a randomised multi-centre phase II trial of the North-Eastern German Society of Gynecological nocology Ovarian Cancer Study Group. J Clin Oncol. 2010;29:242–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Ferrandina G, Ludovisi M, Lorusso D, 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.PubMedCrossRefGoogle Scholar
  97. 97.
    d'Agostino G, Amant F, Berteloot P, et al. Phase II study of gemcitabine in recurrent platinum and paclitaxel-resistant ovarian cancer. Gynecol Oncol. 2003;88:266–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Piccart M, Green J, Lacave A, et al. Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian cancer: a randomised phase II study of the EORTC gynaecological group. J Clin Oncol. 2000;18:1193–202.PubMedGoogle Scholar
  99. 99.
    Rose P, Blessing J, Ball H, et al. A phase II study of docetaxel in platinum resistant ovarian and peritoneal carcinoma: a GOG study. Gynecol Oncol. 2003;88:130–5.PubMedCrossRefGoogle Scholar
  100. 100.
    Sessa C, Braud FD, Perotti A, et al. Trabectedin for women with ovarian carcinoma after treatment with platinum and taxane fails. J Clin Oncol. 2005;23:1867–74.PubMedCrossRefGoogle Scholar
  101. 101.
    Miller D, Blessing J, Krasner C, et al. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a GOG study. J Clin Oncol. 2009;27:2686–91.PubMedCrossRefGoogle Scholar
  102. 102.
    Geest KD, Blessing J, Morris R, et al. Phase II clinical trial of ixabepilone in patients with recurrent or persistant platinum and taxane resistant ovarian or primary peritoneal cancer: a GOG study. J Clin Oncol. 2010;28:149–53.PubMedCrossRefGoogle Scholar
  103. 103.
    Coleman R, Brady W, McMeekin D, et al. A phase II evaluation of nanoparticular, albumin-bound (NAB) paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer: a GOG study. Gyn Oncol. 2011.Google Scholar
  104. 104.
    Seymour M, Mansi J, Gallagher C, et al. Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease. Br J Canc. 1994;69:191–5.CrossRefGoogle Scholar
  105. 105.
    Alici S, Saip P, Eralp Y, et al. Oral etoposide in platinum resistant epithelial ovarian cancer. Am J Clin Oncol. 2003;26:358–62.PubMedGoogle Scholar
  106. 106.
    Watanabe Y, Etoh T, Koike E, et al. Feasibility study of oral cyclophosphamide salvage therapy for the treatment of heavily pretreated patients with recurrent epithelial ovarian cancer. Int J Gynecol Oncol. 2010;15:468–71.Google Scholar
  107. 107.
    Rustin GJ, Nelstrop AE, Crawford M, et al. Phase II trial of oral altretamine for relapsed ovarian carcinoma: evaluation of defining response by serum CA125. J Clin Oncol. 1997;15:172–6.PubMedGoogle Scholar
  108. 108.
    Meier W, Bois AD, Reuss A, et al. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following first line platinum/paclitaxel chemotherapy. A prospectively randomised phase III trial by the AGO ovarian cancer study group. Gynecol Oncol. 2009;114:199–205.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Medical OncologyMount Vernon Cancer CentreMiddlesexUK

Personalised recommendations