PHASE-I STUDY OF TEMOZOLOMIDE IN CHILDREN AND ADOLESCENTS WITH RECURRENT SOLID TUMORS - A REPORT FROM THE CHILDRENS CANCER GROUP

Purpose: The Children's Cancer Group conducted a phase I trial of temo zolomide stratified by prior craniospinal irradiation (CSI), Patients and Methods: Children and adolescents with recurrent or progressive ca ncer were enrolled. Temozolomide was administered orally daily for 5 d ays, with subsequent courses administered every 21 to 28 days after; f ull hematologic recovery. Dose levels tested included 100, 150, 180, 2 15, 245, and 260 mg/m(2) daily. Results: Twenty-seven patients on the non-CSI stratum were assessable for hematologic toxicity. During the f irst three dose levels (100, 150, and 180 mg/m(2) daily), only grades 1 and 2 hematologic toxicity occurred. One patient at 215 mg/m(2) dail y had grade 3 hematologic toxicity. Three of eight patients (38%) trea ted at 245 ta 260 mg/m(2) daily had dose-limiting toxicity (DLT), whic h included both neutropenia and thrombocytopenia, Twenty-two patients on the CSI stratum were assessable for hematologic toxicity. Hematolog ic DLT occurred in one of six patients (17%) at 100 mg/m(2) daily and in two of four patients (50%) at 215 mg/m(2) daily. No nonhematologic DLT occurred; nausea and vomiting occurred in more than half of the pa tients, After two courses of temozolomide, 10 patients had stable dise ase (SD), and three patients had a partial response (PR), one of whom subsequently had a complete response (CR) that persists through 24 mon ths of follow-up. Conclusion: The maximum-tolerated dose (MTD) of temo zolomide for children and adolescents without prior CSI is 215 mg/m(2) daily and for those with prior CSI is 180 mg/m(2) daily for 5 days, w ith subsequent courses that begin on day 28, Temozolomide is well tole rated and should undergo phase II testing in children and adolescents. J Clin Oncol 16:3037-3043. (C) 1998 by American Society of Clinical O ncology.