Most patients with advanced ovarian cancer develop recurrent disease. For those patients who recur at least 6 months after initial therapy, paclitaxel platinum has shown a modest survival advantage over platinum without paclitaxel; however, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. Thus, an alternative regimen without significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer patients.Patients with platinum-sensitive recurrent ovarian cancer were randomly assigned to receive either gemcitabine plus carboplatin or carboplatin alone, every 21 days. The primary objective was to compare progression-free survival (PFS).Three hundred fifty-six patients (178 gemcitabine plus carboplatin; 178 carboplatin) were randomly assigned. Patients received a median of six cycles in both arms. With a median follow-up of 17 months, median PFS was 8.6 months (95% CI, 7.9 to 9.7 months) for gemcitabine plus carboplatin and 5.8 months (95% CI, 5.2 to 7.1 months) for carboplatin. The hazard ration (HR) for PFS was 0.72 (95% CI, 0.58 to 0.90; P = .0031). Response rate was 47.2% (95% CI, 39.9% to 54.5%) for gemcitabine plus carboplatin and 30.9% (95% CI, 24.1% to 37.7%) for carboplatin (P = .0016). The HR for overall survival was 0.96 (95% CI, 0.75 to1.23; P = .7349). While myelosuppression was significantly more common in the combination, sequelae such as febrile neutropenia or infections were uncommon. No statistically significant differences in quality of life scores between arms were noted.Gemcitabine plus carboplatin significantly improves PFS and response rate without worsening quality of life for patients with platinum-sensitive recurrent ovarian cancer.
Background: The combination of carboplatin and paclitaxel is the standard of care for the treatment of ovarian cancer, yet rates of recurrence and death remain high. We performed a prospective randomized phase III study to examine whether sequential administration of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer. Methods: A total of 1308 patients with previously untreated ovarian cancer (International Federation of Gynecology and Obstetrics stages IIB–IV) were randomly assigned to receive six cycles of paclitaxel and carboplatin followed by either four cycles of topotecan (TC-Top; 658 patients) or surveillance (TC; 650 patients) on a 3-week per cycle schedule. The primary endpoint was overall survival, and secondary endpoints were progression-free survival, response rate, toxicity, and quality of life. Time-to-event data were analyzed using the Kaplan–Meier method, and a stratified log-rank test was used to compare distributions between treatment groups. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. Categorical data were compared using a stratified Cochran–Mantel–Haenszel test. All statistical tests were two-sided. Results: Median progression-free survival was 18.2 months in the TC-Top arm versus 18.5 months in the TC arm (stratum-adjusted HR = 0.97 [95% CI = 0.85 to 1.10]; P = .688). Median overall survival was 43.1 months for the TC-Top arm versus 44.5 months for the TC arm (stratum-adjusted HR = 1.01 [95% CI = 0.86 to 1.18]; P = .885). At 3 years, overall survival in both arms was 57% (58.5% in the TC arm and 55.7% in the TC-Top arm). Compared with patients in the TC arm, patients in the TC-Top arm had more grade 3–4 hematologic toxic effects (requiring more supportive care) and more grade 3–4 infections (5.1% versus 2.7%; P = .034) but did not have a statistically significant increase in febrile neutropenia (3.3% versus 3.1%; P = .80). Among patients who had measurable disease (TC, n = 147; TC-Top, n = 145), overall (i.e., complete or partial) response was 69.0% (95% CI = 61.4% to 76.5%) in the TC-Top arm and 76.2% (95% CI = 69.3% to 83.1%) in the TC arm ( P = .166). Conclusions: The sequential addition of topotecan to carboplatin–paclitaxel did not result in superior overall response or progression-free or overall survival. Therefore, this regimen is not recommended as standard of care treatment for ovarian cancer.
Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease.
Advanced or recurrent endometrial cancer (EC) no longer amenable to surgery or radiotherapy is a life-threatening disease with limited therapeutic options left. Eighty percent of ECs express receptors for luteinizing hormone–releasing hormone (LHRH), which can be targeted by AEZS-108 (zoptarelin doxorubicin acetate). This phase 2 trial was performed to assess the efficacy and safety of AEZS-108 in this group of patients.
Methods
Patients had FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) III or IV or recurrent EC, LHRH receptor–positive tumor status, and at least had 1 measurable lesion (Response Evaluation Criteria in Solid Tumors). Prior anthracycline therapy was not allowed. Patients received AEZS-108 as a 2-hour infusion on day 1 of a 21-day cycle. The treatment was continued for a maximum of 6 to 8 cycles. The primary end point was the response rate determined by the Response Evaluation Criteria in Solid Tumors.
Results
From April 2008 to November 2009, 44 patients were included in the study at 8 centers in Germany (AGO) and 3 centers in Bulgaria. Forty-three of these patients were eligible. Two (5%) patients had a complete remission, and 8 (18%) achieved a partial remission. Stable disease for at least 6 weeks was observed in 44%. The median time to progression was 7 months, and the median overall survival was 15 months. The most frequently reported grade 3 or 4 adverse effects were neutropenia (12%) and leucopenia (9%).
Conclusions
AEZS-108, an LHRH-agonist coupled to doxorubicin, has significant activity and low toxicity in women with advanced or recurrent LHRH receptor–positive EC, supporting the principle of receptor-mediated targeted chemotherapy.
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