Docetaxel plus trabectedin appears active in recurrent or persistent ovarian and primary peritoneal cancer after up to three prior regimens: A phase II study of the Gynecologic Oncology Group

Objective. This study aims to estimate the activity of docetaxel 60 mg/m(2) IV over 1 h followed by trabectedin 1.1 mg/m(2) over 3 h with filgrastim, pegfilgrastim, or sargramostim every 3 weeks (one cycle). Methods. Patients with recurrent and measurable disease, acceptable organ function, PS and prior regimens were eligible. A two-stage design was utilized with a target sample size of 35 subjects per stage. Another Gynecologic Oncology Group study within the same protocol queue involving a single agent taxane showed a response rate (RR) of (16%) (90% CI 8.6-28.5%) and served as a hitorical control for direct comparison. The present study was designed to determine if the current regimen had an RR of >= 36% with 90% power. Results. Seventy-one patients were eligible and evaluable (prior regimens: 1=28%, 2=52%, 3=20%). The median number of cycles' was 6 (438 total cycles, range 1-22). The number of patients responding was 21 (30%; 90% CI 21-40%). The odds ratio for responding was 2.2 (90% 1-sided CI 1.07-Infinity). The median progression-free survival and overall survival were 4.5 montlis and 16.9 months, respectively. The median response duration was 6.2 months. Numbers of subjects with grade 3/4 toxicity included neutropenia 7/14; constitutional 8/0; GI (excluding nausea/vomiting) 11/0: metabolic 9/1; pain 6/0. There were no treatment-related deaths nor cases of liver failure. Conclusions. This combination was well tolerated and appears more active than the historical control of single agent taxane therapy in those with recurrent ovarian and peritoneal cancer after failing multiple lines of chemotherapy. Further study is warranted. (C) 2010 Elsevier Inc. All rights reserved.