Tobias Polak

Chapter 7 160 Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Setup From the 4th of August 2005 onwards, an expanded access program was set up to provide access to trabectedin during the regulatory review period. For this report, data from this expanded access program were retrospectively collected up to the 1st of October 2010. Patients with STS following progression of disease after standard therapy were enrolled. Trabectedin was jointly developed by Janssen Research & Development, LLC and PharmaMar S.A. Janssen Research & Development and LLC both funded this study and provided the investigational product. Five of the ten authors have served as scientific advisors and consultants to PharmaMar and Janssen Research & Development and JL and AA are employees of Janssen Research & Development. This study was conducted in accordance with the ethical principles originating in the Declaration of Helsinki and in accordance with ICH Good Clinical Practice guidelines, applicable regulatory requirements, and in compliance with the protocol. Patients The expanded access program was open to patients with various types of advanced soft tissue sarcoma (STS) following progression of disease with standard therapy. Of 1895 enrolled patients, 1803 patients received at least one dose of trabectedin and were included in the analysis population. Patients had a median age of 54 years (range, 16-89). Interventions Patients received trabectedin, a tris tetrahydroisoquinoline alkaloid binding to DNA. By interacting with proteins of the DNA repair machinery, trabectedin disrupts the cell cycle and inhibits cell proliferation. Trabectedin was planned to be administered at an initial dose of 1.5 mg/m2 via a 24-hour intravenous infusion beginning on day 1. Two dose reductions were allowed in the case of toxicity and were based on the investigator’s judgment. The median duration of trabectedin treatment on study was 70 days, representing a median of three treatment cycles; ≥6 cycles were given to 535 (30%) patients. The median trabectedin dose intensity administered was 1.3 mg/ m2 per cycle (86% ideal planned dose). 539 patients experienced a dosing delay and/ or a dose reduction. Outcome The objective response rate, treatment duration, overall survival and safety were evaluated. 807 patients had an evaluable objective response data of which 343 patients reported a stable disease. The median treatment duration was 70 days and the overall survival of patients with

RkJQdWJsaXNoZXIy MTk4NDMw