Abstract
Epithelial ovarian cancer (EOC) is the most common cause of death from gynecological malignancy in the industrialized world. Most patients present with advanced disease and, despite optimal surgical debulking and front-line chemotherapy with platinum- and taxane-based regimens, the majority will relapse. Relapsed EOC is incurable but there are various palliative treatment options. Patients who relapse more than 12 months after primary treatment have a good chance of response to re-challenge with platinum-based chemotherapy. Disease bulk, number of sites of disease, serous histology, type of chemotherapy, baseline hemoglobin, performance status, response to last chemotherapy, and presence of liver metastases also predict treatment outcome in relapsed disease.
A number of new cytotoxic agents have become available over the last decade which are active in relapsed EOC. As single agents, altretamine, anthracyclines, etoposide, gemcitabine, oxaliplatin, taxanes, topotecan and vinorelbine all have response rates of about 20% in patients with relapsed EOC within 12 months of primary treatment. Response rates and perhaps disease-free survival can be increased with the use of combination chemotherapy but toxicity is also increased and, consequently, this approach needs further evaluation in randomized clinical trials. There are no data to support the use of high-dose or intraperitoneal chemotherapy in patients with relapsed EOC outside the context of clinical trials.
Hormonal agents have been used in the treatment of patients with relapsed EOC for some time and, although objective responses are rare, disease stabilization may occur for a prolonged period in a small number of patients. Agents with novel mechanisms of action are emerging from the laboratory into clinical trials. Such agents may also stabilize relapsed disease and include gene therapies, signal transduction inhibitors, anti-angiogenic drugs, matrix metalloproteinase inhibitors and vaccines. None of these therapies, however, are at present part of the standard of care for ovarian cancer.
The study of new agents in patients with relapsed EOC should, when possible, be in the context of randomized clinical trials in which patients are stratified according to known predictors of response to treatment. The issue of when to initiate treatment in women with relapsed disease is difficult as there is no proven benefit to treating patients who are asymptomatic with a rising CA-125 level but no evidence of bulky disease. Patients should not, however, be allowed to develop bulky or multiple sites of disease before treatment is started as the likelihood of response is reduced. Patients should at all times understand and be involved in treatment decisions.
Similar content being viewed by others
References
Blackledge G, Lawton F, Redman C, et al. 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 Cancer 1989; 59: 650–3
Gore ME, Fryatt I, Wiltshaw E, et al. Treatment of relapsed carcinoma of the ovary: with cisplatin or carboplatin following initial treatment with these compounds. Gynecol Oncol 1990; 36: 207–11
Markman M, Rothman R, Hakes T, et al. Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol 1991; 9: 389–93
Gore ME, Fryatt I, Wiltshaw E, et al. Cisplatin/carboplatin cross-resistance in ovarian cancer. Br J Cancer 1989; 60: 767–9
Eisenhauer EA, Vermorken JB, vanGlabbeke M. Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer: a multivariate analysis of 704 patients. Ann Oncol 1997; 8: 963–8
Doyle C, Crump M, Pintilie M, et al. Does palliative chemotherapy palliate? Evaluation of expectations, outcomes, and costs in women receiving chemotherapy for advanced ovarian cancer. J Clin Oncol 2001; 19: 66–74
Manetta A, MacNeill C, Lyter JA, et al. Hexamethylmelamine as a single secondline agent in ovarian cancer. Gynecol Oncol 1990; 36: 93–6
Vergote I, Himmelmann A, Frankendal B, et al. Hexamethylmelamine as secondline therapy in platin-resistant ovarian cancer. Gynecol Oncol 1992; 47: 282–6
Moore DH, Valea F, Crumpler LS, et al. Hexamethylmelamine/altretamine as second-line agent therapy for epithelial ovarian cancer. Gynecol Oncol 1993; 51: 109–12
Schink JC, Harris LS, Grosen ER, et al. Altretamine (Hexalen) an effective salvage chemotherapy after paclitaxel (Taxol) in women with recurrent platinum-resistant ovarian cancer [abstract]. Proc Am Soc Clin Oncol 1995; 14: A770
Rustin GJ, Nelstrop AE, Crawford M, et al. Phase II trial of oral altretamine for relapsed ovarian carcinoma: evaluation of defining response by serum CA-125. J Clin Oncol 1997; 15: 172–6
Markman M, Blessing JA, Moore D, et al. Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory ovarian cancer: a Gynecologic Oncology Group phase II trial. Gynecol Oncol 1998; 69: 226–9
Gordon AN, Fleagle JT, Guthrie D, et al. Recurrent epithelial ovarian carcinoma: a randomised phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 2001; 19: 3312–22
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: 3093–100
Israel VP, Garcia AA, Roman L, et al. Phase II study of liposomal doxorubicin in advanced gynecologic cancers. Gynecol Oncol 2000; 78: 143–7
Markman M, Kennedy A, Webster K, et al. Phase 2 trial of liposomal doxorubicin (40mg/m2) in platinum/paclitaxel refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Gynecol Oncol 2000; 78: 369–72
Hurteloup P, Cappelaere P, Armand JP, et al. Phase II clinical evaluation of 4′epi-doxorubicin. Cancer Treat Rep 1983; 67: 337–41
Simonsen E, Bengtsson C, Hogberg T, et al. A phase II study of the effect of 4′-epi-doxorubicin, administered in high-dose 150mg in 24 hours intravenous infusion in advanced ovarian carcinoma. Proc Eur Conf Clin Oncol 1987; 4: 226
Coleman R, Towlson K, Wiltshaw E, et al. Epirubicin for pretreated advanced ovarian cancer. Eur J Cancer 1990; 26: 850–1
Locatelli MC, D’Antona A, Vinci M, et al. Second-line chemotherapy with epirubicin (EDR) in ovarian carcinoma [abstract]. Ann Oncol 1990; 1: 15
Vermorken JB, Kobierska A, Chevallier B, et al. A phase II study of high-dose epirubicin in ovarian cancer patients previously treated with cisplatin: EORTC Gynecological Cancer Cooperative Group. Ann Oncol 2000; 11: 1035–40
Hansen F, Malthe I, Krog H. Phase II clinical trial of VP-16-213 (etoposide) administered orally in advanced ovarian cancer. Gynecol Oncol 1990; 36: 369–70
Markman M, Hakes T, Reichman B, et al. Phase II trial of chronic low-dose oral etoposide as salvage therapy of platinum-refractory ovarian cancer. J Cancer Res Clin Oncol 1992; 119: 55–7
Marzola M, Zucchetti M, Colombo N, et al. Low-dose oral etoposide in epithelial cancer of the ovary. Ann Oncol 1993; 4: 517–9
Hoskins PJ, Swenerton KD. Oral etoposide is active against platinum-resistant epithelial ovarian cancer. J Clin Oncol 1994; 12: 60–3
DeWit R, vander Burg ME, vanden Gaast A, et al. Phase II study of prolonged oral etoposide in patients with ovarian cancer refractory to or relapsing within 12 months after platinum-containing chemotherapy. Ann Oncol 1994; 5: 656–7
Seymour MT, Mansi JL, Gallagher CJ, et al. Protracted oral etoposide in epithelial ovarian cancer: a phase II study of patients with relapsed or platinum-resistant disease. Br J Cancer 1994; 69: 191–5
Rose PG, Blessing JA, Mayer AR, et al. 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
Lund B, Hansen OP, Theilade K, et al. Phase II study of Gemcitabine (2′,2′-difluorodeoxycytidine) in previously treated ovarian cancer patients. J Natl Cancer Inst 1994; 86: 1530–3
Kaufmann M, Bauknecht T, Jonat W, et al. Gemcitabine (GEM) in cisplatin-resistant ovarian cancer [abstract]. Proc Am Soc Clin Oncol 1995; 14: A758
Friedlander M, Millward MJ, Bell D, et al. A phase II study of gemcitabine in platinum pre-treated patients with advanced epithelial ovarian cancer. Ann Oncol 1998; 9: 1343–8
VonMinckwitz G, Bauknecht T, Visseren-Grul CM, et al. Phase II study of gemcitabine in ovarian cancer. Ann Oncol 1999; 10: 853–5
Silver DF, Piver MS. Gemcitabine salvage chemotherapy for patients with gynaecologic malignancies of the ovary, fallopian tube, and peritoneum. Am J Clin Oncol 1999; 22: 450–3
Coenen M, Berteloot P, Amant F, et al. Gemcitabine in platin-paclitaxel resistant ovarian carcinoma [abstract]. Proc Am Soc Clin Oncol 2000; 19: A1603
Chollet P, Bensmaine MA, Brienza S, et al. Single agent activity of oxaliplatin in heavily pretreated advanced epithelial ovarian cancer. Ann Oncol 1996; 7: 1065–70
Bougnoux P, Dieras V, Petit T, et al. A multicenter phase II study of oxaliplatin (OXA) as a single agent in platinum (PT) or taxanes (TX) pretreated advanced ovarian cancer (AOC): final results [abstract]. Proc Am Soc Clin Oncol 1999; 18: A1422
Piccart MJ, Green JA, Lacave AJ, et al. Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian cancer: a randomised phase II study of the European Organisation for Research and Treatment of Cancer Gynecology Group. J Clin Oncol 2000; 18: 1193–202
Vermorken JB, Gore M, Perren T, et al. Multicenter randomised phase II study of Oxaliplatin (OXA) or topotecan (TOPO) in platinum-pretreated epithelial ovarian cancer (EOC) patients (Pts) [abstract]. Proc Am Soc Clin Oncol 2001; 20: A847
Francis P, Schneider J, Hann L, et al. Phase II trial of docetaxel in patients with platinum-refractory advanced ovarian cancer. J Clin Oncol 1994; 12: 2301–8
Piccart MJ, Gore M, ten Bokkel Huinink WW, et al. Docetaxel: an active new drug for treatment of advanced epithelial ovarian cancer. J Natl Cancer Inst 1995; 87: 676–81
Kavanagh JJ, Kudelka AP, deLeon CG, et al. Phase II study of docetaxel in patients with epithelial ovarian carcinoma refractory to platinum. Clin Cancer Res 1996; 2: 837–42
Kavanagh JJ, Winn R, Steger M, et al. Docetaxel for patients with ovarian cancer refractory to paclitaxel, an update [abstract]. Proc Am Soc Clin Oncol 1999; 18: A1423
Einzig AI, Wiernik PH, Sasloff J, et al. Phase II study and long-term follow-up of patients treated with Taxol for advanced ovarian adenocarcinoma. J Clin Oncol 1992; 10: 1748–53
Kavanagh JJ, Kudelka AP, Edwards CL, et al. A randomised crossover trial of parenteral hydoxyurea vs. high dose taxol in cisplatin/carboplatin resistant epithelial ovarian cancer [abstract]. Proc Am Soc Clin Oncol 1993; 12: A822
Trimble EL, Adams JD, Vena D, et al. Paclitaxel for platinum-refractory ovarian cancer: results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Centre 9103. J Clin Oncol 1993; 11: 2405–10
Markman M, Hakes T, Reichman B, et al. Memorial Sloan Kettering experience with National Cancer Institute treatment referral center protocol 9103: taxol in refractory ovarian cancer [abstract]. Proc Am Soc Clin Oncol 1993; 12: A851
Uziely B, Groshen S, Jeffers S, et al. Paclitaxel (taxol) in heavily pretreated ovarian cancer: antitumour activity and complications. Ann Oncol 1994; 5: 827–33
Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, et al. European-Canadian randomised trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol 1994; 12: 2654–66
Aravantinos G, Skarlos D, Kosmidis P, et al. Taxol in platinum pretreated ovarian cancer patients (preliminary results). Ann Oncol 1994; 5Suppl. 8: 102
Athanassiou A, Pectasides D, Varthalitis I, et al. Taxol patients with cis/carbo platin-refractory ovarian carcinoma [abstract]. Proc Am Soc Clin Oncol 1994; 13: A870
Thigpen JT, Blessing JA, Ball H, et al. Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study. J Clin Oncol 1994; 12: 1748–53
Kohn EC, Sarosy G, Bircher A, et al. Dose intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer. J Natl Cancer Inst 1994; 86: 18–24
Seewaldt VL, Greer BE, Cain JM, et al. Paclitaxel (Taxol) treatment for refractory ovarian cancer: phase II clinical trial. Am J Obstet Gynecol 1994; 170: 1666–71
Gore ME, Levy V, Rustin G, et al. Paclitaxel (taxol) in relapsed and refractory ovarian cancer: the UK and Eire experience. Br J Cancer 1995; 72: 1016–9
Armstrong D, Rowinsky E, Donehower R, et al. A phase II trial of topotecan as salvage therapy in epithelial ovarian cancer [abstract]. Proc Am Soc Clin Oncol 1995; 14: A769
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: 3056–61
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: 1552–7
Swisher EM, Mutch DG, Rader JS, et al. Topotecan in platinum- and paclitaxel-resistant ovarian cancer. Gynecol Oncol 1997; 66: 480–6
ten Bokkel Huinink WW, Gore M, Carmichael J, et al. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol 1997; 15: 2183–93
Bookman MA, Malmstrom H, Bolis G, 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: 3345–52
Hoskins P, Eisenhauer E, Beare S, et al. Randomized phase II study of two schedules of topotecan in previously treated patients with ovarian cancer: a National Cancer Institute of Canada Clinical Trials Group study. J Clin Oncol 1998; 16: 2233–7
Malmstrom H, Ridderheim M, Sorbe B, et al. Salvage treatment of advanced ovarian cancer with hycamtin [abstract]. Proc Am Soc Clin Oncol 1999; 18: A1462
Gore M, Rustin G, Calvert H, et al. A multicentre, randomised, phase III study of topotecan (T) administered intravenously or orally for advanced epithelial ovarian carcinoma. Eur J Cancer 2002; 38: 57–63
Bajetta E, Di Leo A, Biganzoli L, et al. Phase II study of vinorelbine in patients with pretreated advanced ovarian cancer: Activity in platinum-resistant disease. J Clin Oncol 1996; 14: 2546–51
Burger RA, DiSaia PJ, Roberts JA, et al. Phase II trial of vinorelbine in recurrent and progressive epithelial ovarian cancer. Gynecol Oncol 1999; 72: 148–53
Sorensen P, Hoyer M, Jakobsen A, et al. Phase II study of vinorelbine in the treatment of platinum-resistant ovarian carcinoma. Gynecol Oncol 2001; 81: 58–62
Tewey KM, Rowe TC, Yang L, et al. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science 1984; 226: 466–8
ICON 2. A randomised trial of single agent carboplatin against a three-drug combination of CAP (cyclophosphamide, doxorubicin, cisplatin) in women with ovarian cancer. ICON collaborators. International Collaborative Ovarian Neoplasm Study. Lancet 1998; 352: 1571–6
Cersosimo RJ, Hong WK. Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue. J Clin Oncol 1986; 4: 425–39
Gabizon A, Barenholz Y, Bialer M. Prolongation of the circulation time of doxorubicin encapsulated in liposomes containing a polythylene glycol derivatized phospholid: pharmacokinetic studies in rodents and dogs. Pharm Res 1993; 10: 703–8
Gueritte-Vogelein F, Guenard D, Lavelle F, et al. Relationships between the structure of taxol analogues and their antimitotic activity. J Med Chem 1991; 34: 992–8
Ross W, Towe T, Gilsson B, et al. Role of topoisomerase II in mediating epipodophyllotoxin-induced DNA cleavage. Cancer Res 1984; 44: 5857–60
Heinemann V, Hertel W, Grindley GB, et al. Comparison of the cellular pharmacokinetics and toxicity of 2′2′ difluorodeoxyctidine and 1-beta-arabinofurano-sylcytosine. Cancer Res 1998; 48: 4024–31
Rixe O, Ortuzar W, Alvarez M, et al. Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines of the National Cancer Institute’s Anticancer Drug Screen Panel. Biochem Pharmacol 1996; 52: 1855–65
Fink D, Nebel S, Aebi S, et al. The role of DNA mismatch repair in platinum drug resistance. Cancer Res 1996; 56: 4881–6
Hsiang YH, Liu LF. Identification of mammalian DNA topoisomerase I as an intracellular target of the anti-cancer drug camptothecin. Cancer Res 1988; 48: 1722–6
Cros S, Wright M, Moromoto M, et al. Experimental anti-tumour activity of Navelbine. Semin Oncol 1989; 16: 15–20
Andersson H, Boman K, Ridderheim M, et al. An updated analysis of a randomised study of single agent paclitaxel (P) given weekly or every 3 weeks to patients (pts) with ovarian cancer (ov) treated with prior platinum therapy [abstract]. Proc Am Soc Clin Oncol 2000; 19: A1505
Bolis G, Scarf one G, Villa A, et al. A randomised study in recurrent ovarian cancer comparing the efficacy of single agent versus combination chemotherapy, according to time of relapse [abstract]. Proc Am Soc Clin Oncol 1996, 15: A750
Colombo N, Marzola M, Parma G, et al. Paclitaxel vs. CAP (cyclophosphamide, adriamycin, cisplatin) in recurrent platinum sensitive ovarian cancer: a randomised phase II study [abstract]. Proc Am Soc Clin Oncol 1996, 15: A751
Levin L, Hrynuik WM. Dose intensity analysis of chemotherapy regimens in ovarian carcinoma. J Clin Oncol 1987; 5: 756–67
Shpall EJ, Jones RB, Bearman SI, et al. Future strategies for the treatment of advanced EOC using high dose chemotherapy and autologous bone marrow support. Gynecol Oncol 1994; 54: 357–61
Stiff PJ, Bayer R, Kerger C, et al. High-dose chemotherapy with autologous transplantation for persistent/relapsed ovarian cancer: a multivariate analysis of survival for 100 consecutively treated patients. J Clin Oncol 1997; 15: l109–17
Markman M. Intraperitoneal therapy of ovarian cancer. Semin Oncol 1998; 25: 356–60
Markman M, Rowinsky E, Hakes T, et al. Phase I trial of intraperitoneal taxol: a Gynecologic Oncology Group study. J Clin Oncol 1992; 10: 1485–91
Markman M, Reichman B, Hakes T, et al. Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin. J Clin Oncol 1991; 9: 1801–5
Alberts DS, Liu PY, Hannigan EV, 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
Markman M, Bundy BN, Alberts DS, 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 cancer: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol 2001; 19: 1001–7
Gadducci A, Camino F, Chiara S, 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 Oncologico Nord-Ovest. Gynecol Oncol 2000; 76: 157–62
Weiner SA, Alberts DS, Surwit EA, et al. Tamoxifen therapy in recurrent epithelial ovarian carcinoma. Gynecol Oncol 1987; 27: 208–13
Hatch KD, Beecham JB, Blessing JA, et al. Responsiveness of patients with advanced ovarian carcinoma to tamoxifen: a Gynecologic Oncology Group study of second-line therapy in 105 patients. Cancer 1991; 68: 269–71
Markman M, Iseminger KA, Hatch KD, et al. Tamoxifen in platinum-refractory ovarian cancer: A Gynecologic Oncology Group Ancillary Report. Gynecol Oncol 1996; 62: 4–6
Shirey DR, Kavanagh Jr JJ, Gershenson DM, et al. Tamoxifen therapy of epithelial ovarian cancer. Obstet Gynecol 1987; 27: 208–13
Ahlgren JD, Ellison NM, Gottlieb RJ, et al. Hormonal palliation of chemoresistant ovarian cancer: three consecutive phase II trials of the Mid-Atlantic Oncology Program. J Clin Oncol 1993; 11: 1957–68
Bruckner HW, Motwani BT. Treatment of advanced refractory ovarian carcinoma with a gonadotrophin-releasing hormone analogue. Am J Obstet Gynecol 1989; 161: 1216–8
Kavanagh JJ, Roberts W, Townsend P, et al. Leuprolide acetate in the treatment of refractory or persistent epithelial ovarian cancer. J Clin Oncol 1989; 7: 115–8
Lind MJ, Cantwell BM, Millward MJ, et al. A phase II trial of goserelin (Zoladex) in relapsed epithelial ovarian cancer. Br J Cancer 1992; 65: 621–3
Miller DS, Brady MF, Barrett RJ. A phase II trial of leuprolide acetate in patients with advanced epithelial ovarian carcinoma: a Gynecologic Oncology Group study. Am J Clin Oncol 1992; 15: 125–8
Marinaccio M, D’Addario V, Serrati A, et al. Leuprolide acetate as a salvage therapy in relapsed epithelial ovarian cancer. Eur J Gynaecol Oncol 1998; 17: 286–8
Mangioni C, Franceschi S, LaVecchia C, et al. High-dose medroxyprogesterone actate (MPA) in advanced epithelial ovarian cancer resistant to first- or second-line chemotherapy. Gynecol Oncol 1981; 12: 314–8
Hamerlynck JV, Maskens AP, Mangioni C, et al. Phase II trial of medroxyprogesterone acetate in advanced ovarian cancer: an EORTC Gynecological Cancer Cooperative Group study. Gynecol Oncol 1985; 22: 313–6
Malfetano J, Beecham JB, Bundy BN, et al. A phase II trial of medroxyprogesterone acetate in epithelial ovarian cancers: a Gynecologic Oncology Group study. Am J Clin Oncol 1993; 16: 149–51
Berchuck A, Kohler MF, Marks JR, et al. The p53 tumour suppressor gene frequently is altered in gynaecologic cancers. Am J Obstet Gynecol 1994; 170: 246–52
Righetti SC, Delia Torre G, Pilotti S, et al. A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma. Cancer Res 1996; 56: 689–93
Wiman KG. New p53-based anti-cancer therapeutic strategies. Med Oncol 1998; 15: 222–8
Wen SF, Mahavni V, Quijano E, et al. Evidence of p53 gene transfer and its biological activities in ovarian cancer patients receiving multiple cycles of recombinant adenovirus expressing wild-type p53 [abstract]. Proc Am Soc Clin Oncol 2001; 20: A849
Hasenburg A, Tong XW, Fischer DC, et al. Adenovirus-mediated thymidine kinase gene therapy in combination with topotecan for patients with recurrent ovarian cancer: 2.5-year follow-up. Gynecol Oncol 2001; 83: 549–54
Bookman MA. Biological therapy of ovarian cancer: current directions. Semin Oncol 1998; 25: 381–96
Pietras RJ, Fendly BM, Chazin VR, et al. Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. Oncogene 1994; 9: 1829–38
Slamon D, Leyland-Jones B, Shark S, et al. Addition of herceptin to first line chemotherapy for HER-2 overexpressing metastatic breast cancer markedly increases anticancer activity a randomised controlled phase III trial [abstract]. Proc Am Soc Clin Oncol 1998; 17: A212
Hirte HW, Vergote IB, Jeffrey JR, et al. An international multicentre Phase III study of BAY 12-9566 (BAY) versus placebo in patients (Pts) with advanced ovarian cancer (OVCA) responsive to primary surgery/paclitaxel + platinum containing chemotherapy (CT) [abstract]. Proc Am Soc Clin Oncol 2001; 20: A843
D’Amato RJ, Loughnan MS, Flynn E,et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994; 91: 4082–5
Abramson N, Stokes P. Ovarian and peritoneal papillary-serous carcinoma: pilot study using thalidomide [abstract]. Proc Am Soc Clin Oncol 2001; 20: A2466
Eisen T, Boshoff C, Mak I, et al. Continuous low dose thalidomide: a phase II study in advanced melanoma, renal cell, ovarian and breast cancer. Br J Cancer 2000; 82: 812–7
Wagner U, Kohler S, Reinartz S, et al. Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody acal25: immune responses and survival in palliative treatment. Clin Cancer Res 2001; 7: 1154–62
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Larkin, J.M.G., Gore, M.E. Chemotherapy Options for Patients with Relapsed Epithelial Ovarian Cancer. Am J Cancer 1, 205–216 (2002). https://doi.org/10.2165/00024669-200201030-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00024669-200201030-00005