Increasing single epirubicin doses in advanced soft tissue sarcomas

To evaluate the maximum-tolerated dose and the clinical efficacy of epirubicin in patients with advanced soft tissue sarcoma.

Sixty-one patients were treated at three different epirubicin dose levels: 140 mg/m(2) (six patients), 160 mg/m(2) (52 patients), and 180 mg/m(2) (three patients). Cycles were repeated every 3 weeks for a maximum of eight cycles. The first two dose levels proved to be feasible and safe without dose-limiting toxicity (DLT). Because the first three patients entering the third dose level experienced DLT, subsequent patients received the next lower dose level.

The overall response rate was 44% (95% confidence interval, +/- 12%), with six complete (10%) and 21 partial (34%) responses. Responses seemed related to epirubicin dose level, because the response rate was 17%, 44%, and 100% for the three dose levels (chi(2) test for trend, P =.02). Median response duration, median time to progression, and median overall survival were 10, 8, and 15 months, respectively. Myelosuppression was the most frequent side effect, with grade 3 or 4 neutropenia occurring in 79% of the patients; 31% of patients were febrile. Nonhematologic toxicity was mainly grades 1 and 2. The mean epirubicin dose-intensity was 49 mg/m(2) per week.

The third epirubicin dose level (180 mg/m(2)) was the maximum-tolerated dose. The recommended drug dose for clinical use is 160 mg/m(2) every 3 weeks with hematopoietic support. Single high-dose epirubicin is effective as first-line treatment and should be preferentially used whenever a high response rate is important to allow the resection of an otherwise unresectable disease or whenever it might result in a significant symptomatic benefit.