A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma - A study by the Spanish group for research on sarcomas

BACKGROUND. The objective of this study was to evaluate the activity and toxicity of temozolomide given as an extended schedule in patients with advanced sarcoma. METHODS. Forty-nine patients with pretreated soft tissue sarcoma (the STS arm) and 18 patients with previously untreated gastrointestinal stromal tumor (the GIST arm) were enrolled onto a 2-arm, multicenter, Phase II study between November 1999 and July 2001. Temozolomide was administered on a 6-week, continuous, oral schedule at a dose of 75 mg/m(2) per day in 41 patients and, after an amendment, at a dose of 100 mg/m(2) per day in 22 patients. RESULTS. Among 45 eligible patients in the STS arm, there were 7 partial responses, for an overall response rate of 15.5% (95% confidence interval [95% CI], 5-26%). Responses were seen in 5 of 11 patients who had gynecologic leiomyosarcoma. The median response duration was 12.5 months (range, 3.9-58.0 mos). In 4 patients, response lasted > 1 year, and 2 of those patients remained progression free for > 3 years. The median time to progression was 2.2 months (95% CI, 1.8-2.5 mos), and the median overall survival was 8.1 months (95% CI, 5.6-10.6 mos). progression-free survival rates at 3 months and 6 months were 39.5% and 26%, respectively. In the GIST arm, no responses were noted. Grade 3-4 granulocytopenia, thrombocytopenia, and anemia were observed in 6 patients, 5 patients, and 7 patients, respectively. The most common nonhematologic toxicities were emesis and fatigue. CONCLUSIONS. Temozolomide at the extended schedule was tolerated well and had activity in patients with pretreated soft tissue sarcomas, and especially among patients with gynecologic leiomyosarcoma.