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

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.

• Authors: Darren R Hargrave, Eric Bouffet, Janet Gammon, Nauman Tariq, Ron M Grant, Sylvain Baruchel
• Journal: Cancer (Cancer) Vol. 95 Issue 6 Pg. 1294-301 (Sep 15 2002) ISSN: 0008-543X [Print] United States
• PMID: 12216098 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 American Cancer Society.

Chemical References

• Antineoplastic Agents
• Nitrosourea Compounds
• Organophosphorus Compounds
• fotemustine

Topics

• Adolescent
• Anemia (chemically induced)
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Brain Neoplasms (drug therapy)
• Child
• Child, Preschool
• Ependymoma (drug therapy)
• Female
• Humans
• Infant
• Injections, Intravenous
• Male
• Medulloblastoma (drug therapy)
• Neutropenia (chemically induced)
• Nitrosourea Compounds (administration & dosage, adverse effects, therapeutic use)
• Organophosphorus Compounds (administration & dosage, adverse effects, therapeutic use)
• Sarcoma (drug therapy)
• Thrombocytopenia (chemically induced)
• Treatment Outcome