PILOT-STUDY OF HIGH-DOSE ZORUBICIN IN ADV ANCED SOFT-TISSUE SARCOMA IN ADULTS

High-dose anthracyclines, doxorubicin 75 mg/m(2) and epirubicin 150-18 0 mg/m(2) are the most active drugs in the treatment of advanced soft tissue sarcoma. These dosages are associated with significant hematolo gical toxicity for both drugs and a high risk of cardiotoxicity for ca rdiotoxicity for doxorubicin. The aim of this pilot study was to inves tigate the activity of zorubicin in advanced soft tissue sarcoma, with a dosage supposed to be equihematotoxic to epirubicin 180 mg/m(2). Tw enty of 21 patients who had been included in the study were evaluable for response, 15 males and five females, median age 41 (range 20-67) g ears. All patients received zorubicin 600 mg/m(2) per cycle divided in 3 days, the intercycle interval being 4 weeks. The cardiac function w as monitored by determinations of left ventricular ejection fraction b efore each cycle. Therapeutic response was the following: 2/20 patient s (10%) complete response, 6/20 (30%) partial response, 6/20 (30%) sta ble disease and 6/20 (30%) progressive disease, the overall response r ate being 8/20 (40%). Complete responses were observed in a patient wi th undifferentiated sarcoma of the mediastinum and in a patient with u nresectable angiosarcoma of subcutaneous tissues. The major toxicity w as hematological, with granulocytopenia grade 4 occurring in 42/66 cyc les, and the nadir on day la of the treatment cycle. Nine of 66 cycles were complicated by febrile neutropenia and stomatitis of any grade w as recorded in only 1/66 cycles. No cumulative cardiotoxicity was obse rved up to a total cumulative zorubicin dose of 3,000 mg/m(2).