FRACTIONATED HIGH-DOSE CYCLOPHOSPHAMIDE FOR ADVANCED PEDIATRIC SOLID TUMORS

Purpose: The objective of this study was to determine the tolerance an d toxicities of high-dose cyclophosphamide (CPA) at 7 g/m(2) given in four fractions over 8 h in children with advanced solid tumors. Patien ts and Methods: Twenty children aged 11/2-19 years (median, 12 years) received 24 courses of high-dose CPA at 7 g/m(2) for the treatment of advanced malignant solid tumor. CPA was given in four l-h infusions of 1.75 g/m(2) each, with 1 h of rest between each dose. MESNA was used as a uroprotective agent and was continued for 24 h after the final do se of CPA. With only one exception, all patients were discharged at th e end of MESNA infusion and received granulocyte colony-stimulating fa ctor, prophylactic ciprofloxacin, and co-trimoxazole. Results: Severe but transient myelosuppression was observed. The median time to neutro phil and platelet recovery was 17 and 19 days, respectively. Fever dev eloped after 13 of the 24 courses, and hospitalization was required. E xtramedullary toxicities were mild. No patient showed cardiomyopathy o r hemorrhagic cystitis. Forty-six percent of the courses were managed entirely on an outpatient basis. Objective tumor response was seen in five patients. Conclusions: CPA at 7 g/m(2) is well tolerated by child ren with advanced malignancies and should be considered in earlier pha ses of antineoplastic therapy.