AMBULATORY CONTINUOUS-INFUSION IFOSFAMIDE WITH ORAL ETOPOSIDE IN ADVANCED SARCOMAS

Background. Chemotherapy given by continuous infusion may have differe nt toxicity profiles and different degrees of therapeutic efficacy tha n when given by bolus administration. The potential therapeutic benefi ts of continuous infusion chemotherapy and the advantages of outpatien t treatment led us to study a continuous infusion of ifosfamide with m esna and oral etoposide. Methods. The authors performed a Phase I-II t rial in which 9 g/m2 ifosfamide was administered for 6 days and 10.5 g /m2 mesna was administered for 7 days, both by continuous infusion, in combination with 50 mg/m2/d oral etoposide for 8 days in 21 patients with sarcomas or other solid tumors. Courses were repeated every 28 da ys. Results. A total of 65 treatment cycles were given. Only six patie nts required hospitalization for treatment, all because of an initial poor performance status, and most carried out normal activities or. an ambulatory basis. Treatment was stopped during the first course in fi ve patients because of central nervous system toxicity, each with a po or pretreatment performance status; neurologic recovery was complete i n each patient. The dose of etoposide was decreased by 20% in 11 patie nts and unchanged in 7 following the first treatment. Hematologic toxi city was predominantly manifested by leukopenia. An absolute neutrophi l count less than 500 neutrophils/mul occurred in 22 of 50 cycles; thr ombocytopenia (platelets less than 100,000/mul) was seen in two patien ts, requiring platelet transfusion in one. Neutropenic fevers occurred in 13 of 65 cycles; in 4 of these, cultures demonstrated a bacterial infection. Nausea and vomiting were mild. Objective responses occurred in 6 of 16 patients with soft tissue sarcomas (6 partial responses [P R]) (95% confidence interval, 15-65%), and 3 of 5 bone sarcomas, all o f whom had been previously treated with doxorubicin and dacarbazine. C onclusions. The authors concluded that ifosfamide and mesna given by a mbulatory continuous intravenous infusion with wearable pump systems i n combination with oral etoposide was well tolerated and showed substa ntial anti-tumor activity. This combination represents a rational ther apeutic approach to patients with advanced soft tissue sarcomas and ma y have application to other malignancies.