PurposeThis randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).Patients and MethodsPatients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.ResultsOverall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.ConclusionTo our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.

BackgroundWe evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma.MethodsWe performed an open-label one-arm, two-stage, phase II study of 25 mg of oral exemestane in 51 patients with advanced (FIGO stage III-IV) or relapsed endometrioid endometrial cancer. Patients were stratified into subsets of estrogen receptor (ER) positive and ER negative patients.ResultsRecruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual. In the ER positive patients, we observed an overall response rate of 10%, and a lack of progression after 6 months in 35% of the patients. No responses were registered in the ER negative patients, and all had progressive disease within 6 months. For the total group of patients, the median progression free survival (PFS) was 3.1 months (95% CI: 2.0-4.1). In the ER positive patients the median PFS was 3.8 months (95% CI: 0.7-6.9) and in the ER negative patients it was 2.6 months (95% CI: 2.1-3-1). In the ER positive patients the median overall survival (OS) time was 13.3 months (95% CI: 7.7-18.9), in the ER negative patients the corresponding numbers were 6.1 months (95% CI: 4.1-8.2). Treatment with exemestane was well tolerated.ConclusionTreatment of estrogen positive advanced or recurrent endometrial cancer with exemestane, an aromatase inhibitor, resulted in a response rate of 10% and lack of progression after 6 months in 35% of the patients.Trial registrationTrial identification number (Clinical Trials.gov): NCT01965080.Nordic Society of Gynecological Oncology: NSGO–EC–0302.EudraCT number: 2004-001103-35.

Adding anthracyclin to conventional platinum-based chemotherapy of ovarian cancer has been found to improve survival. The aim of this study was to evaluate the effect on survival on adding epirubicin to the standard treatment with carboplatin and paclitaxel. Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal, or peritoneal cancer FIGO stage IIB-IV were enrolled. They were randomized to receive six to nine cycles of paclitaxel (175 mg/m 2 , 3 h iv) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m 2 iv prior to paclitaxel) on a 3-weekly schedule. The primary end point was progression-free survival, and 542 progression events were required to detect a hazard ratio of 0.786 or less. Patient characteristics were similar across the treatment arms. Residual disease less than 1 cm at surgery with no measurable disease before chemotherapy was reported in 328 patients (37%), with 159 in the TEC arm and 169 in the TC arm. A total of 63 patients had to be withdrawn from the study: 20 due to ineligibility, 32 due to hypersensitivity reaction to paclitaxel during the first or second course, and 11 due to withdrawal of informed consent, leaving 824 patients for the survival analysis. The median follow-up is 30 months for patients still alive. Progressive disease has been reported for 573 patients, and 326 have died. In the total group of patients, the median time to progression was 17.2 months in the TEC arm and 16.3 in the TC arm (P ¼ 0.99). In the group with residual tumor of 1 cm or less, the median time to progression was 24.7 months in the TEC arm and 24.4 months in the TC arm (P ¼ 0.94). In patients with more than 1 cm of residual tumor, the median time to progression in the TEC arm was 14.6 months and 13.8 months in the TC arm (P ¼ 0.75). The median overall survival has not yet been reached. The addition of epirubicin to the standard carboplatin and paclitaxel treatment did not improve progression-free survival. The evaluation of effect on long-term survival awaits further follow-up.