Trabectedin in pre-treated patients with advanced or metastatic soft tissue sarcoma: a phase II study evaluating co-treatment with dexamethasone.

PURPOSE: This study assesses the efficacy, toxicity and pharmacokinetic profile of trabectedin with or without prophylactic dexamethasone co-treatment in patients with recurrent advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: Patients were randomized to receive trabectedin as a 3-h infusion every 3 weeks with dexamethasone or placebo in the first cycle, with the alternate in the second cycle and with the patient's choice subsequently. Due to toxicity, the randomized design was modified to open-label to make dexamethasone mandatory and the initial dose (1,650 μg/m(2)) was reduced to 1,500 μg/m(2) and then to 1,300 μg/m(2).
RESULTS: Forty-one patients were enrolled and 35 were evaluable for efficacy. One partial response and 18 disease stabilizations were found. The median PFS and OS were 2.1 and 10.2 months, respectively, with the 3- and 6-month PFS rates indicating activity in pretreated STS. Twenty-three and 27 patients developed transient asymptomatic grade 3/4 AST and ALT elevation, respectively, and 21 patients had grade 3/4 neutropenia. Dose reduction from 1,650 μg/m(2) to 1,300 μg/m(2) decreased the incidence of grade 3/4 thrombocytopenia (26% vs. 0%), neutropenia (51% vs. 25%) and AST increase (76% vs. 25% of patients). Four patients died due to drug-related toxicities (3 with placebo). The total body clearance of trabectedin was 28% higher and half-life was 21% lower with dexamethasone compared to placebo, with no differences in volume of distribution.
CONCLUSIONS: Trabectedin has confirmed activity in patients with pretreated STS. This study shows that co-treatment with dexamethasone improves the safety of trabectedin by reducing drug-induced hepatotoxicity and myelosuppression.

RCT Entities:   Population Interventions Outcomes