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

✍ Scribed by Darren R. Hargrave; Eric Bouffet; Janet Gammon; Nauman Tariq; Ron M. Grant; Sylvain Baruchel

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 184 KB
• Volume: 95
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/cncr.10814

✦ Synopsis

Abstract

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. Cancer 2002;95:1294–301. © 2002 American Cancer Society.

DOI 10.1002/cncr.10814