Phase I study of fotemustine in pediatric patients with refractory brain tumors
Version of Record online: 5 SEP 2002
Copyright © 2002 American Cancer Society
Volume 95, Issue 6, pages 1294–1301, 15 September 2002
How to Cite
Hargrave, D. R., Bouffet, E., Gammon, J., Tariq, N., Grant, R. M. and Baruchel, S. (2002), Phase I study of fotemustine in pediatric patients with refractory brain tumors. Cancer, 95: 1294–1301. doi: 10.1002/cncr.10814
- Issue online: 5 SEP 2002
- Version of Record online: 5 SEP 2002
- Manuscript Accepted: 6 MAY 2002
- Manuscript Revised: 17 MAR 2002
- Manuscript Received: 16 JAN 2002
- Servier Research International, France
- Phase I;
- brain tumors
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.
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/m2. Toxicity and response data were monitored closely.
Fifteen evaluable patients entered the study and received a total of 45 courses of fotemustine (dose range, 100–175 mg/m2). 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/m2 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.
Fotemustine administered at a dose of 150 mg/m2 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. Cancer 2002;95:1294–301. © 2002 American Cancer Society.