This is an archive of papers published by the staff and faculty of Fox Chase Cancer Center. For questions about content, please contact Talbot Research Library
Last updated on
Blay JY , von Mehren M , Samuels BL , Fanucchi MP , Ray-Coquard I , Buckley B , Gilles L , Lebedinsk C , Elsayed YA , Le Cesne A
Phase I Combination Study of Trabectedin and Doxorubicin in Patients with Soft-Tissue Sarcoma
Clinical Cancer Research. 2008 Oct;14(20) :6656-6662
AbstractPurpose: To determine the dose of trabectedin plus doxorubicin with granulocyte colony-stimulating factor support associated with manageable neutropenia and acceptable dose-limiting toxicities (DLT) in patients with recurrent or persistent soft-tissue sarcoma. Methods: In this phase I, open-label, multicenter trial, patients previously treated with 0-1 prior chemotherapy regimens excluding doxorubicin, an Eastern Cooperative Oncology Group performance status 0-1, and adequate organ function received a 10- to 15-min i.v. infusion of doxorubicin 60 mg/m(2) immediately followed by a 3-h i.v. infusion of trabectedin 0.9 to 1.3 mg/m(2) on day 1 of a 3-week cycle. Because four of the first six patients experienced DLT-defining neutropenia during cycle 1, all subsequent patients received primary prophylactic granulocyte colony-stimulating factor. The maximum tolerated dose was the highest dose level with six or more patients in which less than one-third of the patients experienced severe neutropenia or DLT. Blood was collected during cycle 1 for pharmacokinetic analyses. Adverse events, tumor response, and survival were assessed. Results: Patients (N = 41) received a median of six cycles of treatment (range, 2-13). The maximum tolerated dose was trabectedin 1.1 mg/m(2) and doxorubicin 60 mg/m(2). Common grade 3/4 treatment-emergent adverse events were neutropenia (71%), alanine aminotransferase increase (46%), and thrombocytopenia (37%). Overall, 5 (12%) patients achieved a partial response and 34 (83%) maintained stable disease. Median progression-free survival was 9.2 months. Doxorubicin and trabectedin pharmacokinetics were not altered substantially with concomitant administration. Conclusion: The combination of doxorubicin 60 mg/m(2) followed by trabectedin 1.1 mg/m(2) every 21 days is safe and active in patients with soft-tissue sarcoma.
NotesBlay, Jean-Yves 39 AMER ASSOC CANCER RESEARCH; 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA 364TZ