Phase I study of fotemustine in pediatric patients with refractory brain tumors.

Background: Fotemustine is a nitrosourea with theoretic and preclinical advantages over the original analogs, carmustine and lomustine, in the treatment of brain tumors. This is the first pediatric Phase I study of fotemustine.

Methods: Patients younger than 21 with recurrent/resistant brain tumors were enrolled in a conventional Phase I study. Fotemustine was administered intravenously every 3 weeks at increasing dose levels starting at 100 mg/m(2). Toxicity and response data were monitored closely.

Results: Fifteen evaluable patients entered the study and received a total of 45 courses of fotemustine (dose range, 100-175 mg/m(2)). Myelosuppression was observed, with the dose-limiting toxicity being Grade 4 neutropenia and thrombocytopenia. Toxicity was delayed and cumulative. The maximum tolerated dose was 150 mg/m(2) every 3 weeks. There were three documented radiologic responses (20% of patients) comprising one partial response and two minor responses in patients with a sarcoma, medulloblastoma, and ependymoma, respectively.

Conclusions: Fotemustine administered at a dose of 150 mg/m(2) every 3 weeks is well tolerated in children and has antitumor activity in several brain tumors. This is the first dedicated Phase I study of a single agent nitrosourea in a pediatric population. More comparative studies should be undertaken to define the optimum nitrosourea analog for use in children with brain tumors.