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

• Published in: Gynecologic oncology Vol. 124; no. 1; pp. 48 - 52
• Main Authors: Monk, Bradley J, Blessing, John A, Street, Daron G, Muller, Carolyn Y, Burke, James J, Hensley, Martee L
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2012
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating - adverse effects; Antineoplastic Agents, Alkylating - therapeutic use; Dioxoles - adverse effects; Dioxoles - therapeutic use; Disease-Free Survival; Drug Administration Schedule; Female; Hematology, Oncology and Palliative Medicine; Humans; Infusions, Intravenous; Leiomyosarcoma; Leiomyosarcoma - drug therapy; Leiomyosarcoma - pathology; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Obstetrics and Gynecology; Prospective Studies; Survival Rate; Tetrahydroisoquinolines - adverse effects; Tetrahydroisoquinolines - therapeutic use; Trabectedin; Uterine cancer; Uterine Neoplasms - drug therapy; Uterine Neoplasms - pathology; Trabectedin; Uterine cancer; Leiomyosarcoma
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2011.09.019

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.