A phase II evaluation of trabectedin in the treatment of advanced, persistent, or recurrent uterine leiomyosarcoma: a gynecologic oncology group study

Abstract

Objective: To estimate activity and safety of trabectedin 1.5 mg/m2 IV over 24 hours every 3 weeks (1 cycle) in uterine leiomyosarcoma.

Methods: Patients with chemotherapy naive, advanced, persistent or recurrent uterine leiomyosarcoma, acceptable organ function and PS≤2 were eligible. A two-stage design was utilized. Three responses were required in the first stage to initiate the second stage; the target sample size was 40 for the combined stages. If the true response rate was 10%, the study design provided a 95% chance of correctly classifying the treatment as "inactive." Conversely, if the true response rate was 30%, then the average probability of correctly classifying the treatment as active would be 90%.

Results: Twenty patients were eligible and evaluable. The median number of cycles was 10 (123 total cycles, range 2-29). The number of patients with partial responses was 2 (10%; 95% confidence interval of 1.2%-31.7%). Response durations were 3.3 and 5.7 months. Ten patients had stable disease (50%). The median progression-free survival (PFS) and overall survival were 5.8 months and greater than 26.1 months (median not reached), respectively. Observed grade 3/4 toxicity included: neutropenia 16/20 (1 infection); thrombocytopenia 3/20; metabolic 3/20; anemia, gastrointestinal and vascular 1/20 each. There were no treatment related deaths nor cases of liver failure.

Conclusions: Although a second stage of accrual was not indicated based on the overall response rate, the drug was well tolerated.

Conflict of interest statement

CONFLICT OF INTEREST

Dr. Bradley Monk has an honoraria and research funding from Johnson & Johnson. All other co-authors have no conflicts of interest to declare.

Copyright © 2011 Elsevier Inc. All rights reserved.

Figures

Figure 1

Kaplan-Meier plots demonstrating overall and progression-free survival (PFS) for the 20 patients in the study population (GOG 87M)

Figure 2

Kaplan-Meier plots demonstrating progression-free survival (PFS) for the 20 patients in the study population (GOG 87M) compared to other single agent studies in the GOG protocol 87 series studying cytotoxic agents