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.
Hargrave
Darren R
DR
New Agents and Innovative Therapy Program, The Hospital for Sick Children, University of Toronto, Ontario, Canada.
Bouffet
Eric
E
Gammon
Janet
J
Tariq
Nauman
N
Grant
Ron M
RM
Baruchel
Sylvain
S
D000293:Adolescent; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000188:drug therapy; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012509:Sarcoma / Q000188:drug therapy; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; C054368:fotemustine