Phase II Study of Temozolomide and Thalidomide in Patients with Unresectable or Metastatic Leiomyosarcoma

9029 Background: Our previous phase II study of temozolomide in sarcoma suggested temozolomide has modest activity in patients with leiomyosarcoma (Cancer 2003;9:1942). The combination of temozolomide and the anti-angiogenic agent thalidomide is reported to show promising activity in other tumors. The objective of this study was to assess the efficacy of temozolomide and thalidomide in leiomyosarcoma patients with unresectable or metastatic disease. Methods: Patients with histologically-confirmed advanced-stage leiomyosarcoma were enrolled on this single-institution Phase II trial. Prior systemic chemotherapy (0–3 regimens) was allowed. Temozolomide (150mg/m2/day for 7 days every other week) was administered with concomitant thalidomide (200mg/day). Treatment was continued until unacceptable toxicity or disease progression occurred. Results: Twenty-three eligible patients (median age 60) were enrolled. Nineteen (83%) had received prior systemic chemotherapy. There was one partial response (PR), no complete responses and 5 patients had stable disease (SD) that lasted for more than 4 months. The average time to progression for the PR and SD patients was 9.3 months. One patient had a PR lasting 23 months. The median time to progression for non-responders was 6 weeks. Ten of 21 patients required dose reduction or discontinuation of thalidomide, including 4 of the 6 patients with either PR or SD. There were no treatment related deaths or National Cancer Institute Grade 4 toxicities. Grade 3 toxicities included neutropenia, anemia, emesis, fatigue (4% each), pain (10%), and neurologic toxicity (13%). Conclusion: This combination of temozolomide and thalidomide provided disease stabilization in a subset of patients with metastatic leiomyosarcoma. In this study, thalidomide was poorly tolerated and may have contributed to the toxicity of the regimen. We hypothesize that temozolomide is the active agent in this regimen. Further studies of temozolomide as first or second-line treatment in advanced leiomyosarcoma are warranted. No significant financial relationships to disclose.