TREATMENT OF ADVANCED, HIGH-GRADE SOFT-TISSUE SARCOMA WITH IFOSFAMIDEAND CONTINUOUS-INFUSION ETOPOSIDE

A total of 33 patients (median age, 44 years) with high-grade, adult s oft-tissue sarcoma were treated with etoposide given at 600 mg/m(2) in a 72-h continuous infusion and ifosfamide given at 1500 mg/m(2) per d ay for 3 days every 3 weeks. Dose escalation/reduction was protocolled depending on the level of hematological toxicity observed in the prec eding course. Overall, 90% of patients had metastatic disease, and the most common histologies were malignant fibrous histiocytoma and leiom yosarcoma. A median of 5 (range, 1-9) courses were given. Of 30 patien ts who were evaluable for response, 12 (40%) obtained a partial remiss ion, and the median time to progression was 8 (range, 4-13) months. Gr ade 3-4 leukopenia and thrombocytopenia were seen after 89% and 8% of the courses, respectively; neutropenic fever was seen in half of the p atients (15% of courses); and 32% of courses had to be postponed by 7 days or more due to myelosuppression. Dose reduction to below the stan dard had to be performed in 46% of courses, and dose escalation was ac hieved in only 13%. The reduced toxicity seen after the addition of gr anulocyte colony-stimulating factor (G-CSF) in five patients indicates that growth-factor support may enhance the dose intensity of the regi men. The results indicate significant activity for this regimen in adu lt soft-tissue sarcoma, which may in part be a result of the escalated dose and prolonged mode of administration of the phase-specific agent etoposide. As a result of this pilot series, a phase II study with if osfamide, etoposide, and G-CSF in advanced adult soft-tissue sarcoma h as been initiated by the Scandinavian Sarcoma Group.