[A phase II study of epirubicin in acute leukemia: a cooperative group study]

A new doxorubicin analogue, epirubicin (EPI), has been evaluated in 11 institutions throughout Japan in a phase II study in patients with acute leukemia. A total of 41 patients were entered into this study between January 1983 and July 1985, and 34 were considered evaluable. Two patients were added for evaluation of toxicity. There were 25 males and 9 females with a median age of 43 years. Of the 34 evaluable patients, 24 had previously been treated with intensive combination chemotherapy, 21 with anthracyclines. The remaining ten were previously untreated patients. Underlying diseases were acute lymphocytic leukemia (ALL) in 15, acute non-lymphocytic leukemia (ANLL) in 17 and blastic crisis of chronic myelogenous leukemia (CML/BC) in 2. EPI was administered intravenously in two schedules, a high-dose regimen consisting of 24 to 60 mg/m2/day for 3 to 5 days and a low-dose regimen involving 11-17 mg/m2/day for 5 to 8 days. Responses were obtained in 5 (33.3%) of 15 patients with ALL, 3 of these attaining complete remission, 2 (11.8%) of 17 patients with ANLL and one (50.0%) of 2 patients with CML/BC. Out of the 21 patients who had received previous anthracyclines, 4 (19.1%) attained responses. Also, responses were obtained in 23.5% with the higher doses as well as 24% with the lower doses. The remission duration of responders was 1, 1, 3, 3, 3, 16+, 17 and 26 weeks, respectively. The major non-hematologic toxicity was stomatitis which occurred in 15 patients, in 11 of whom the symptoms were severe (Grade 3 or 4). This stomatitis was thought to be the dose limiting factor. On the basis of the above observations, we concluded that EPI was active against acute leukemia, especially ALL. Stomatitis was considered to be the dose-limiting factor, especially in the high-dose regimen. Toxicity was tolerable in the low-dose regimen.