A phase I trial of fazarabine in refractory pediatric solid tumors. A Pediatric Oncology Group study.
Fazarabine is a synthetic analog of cytosine arabinoside and 5-azacytidine that incorporates structural features of both compounds. Xenograft studies showed good activity against a variety of transplanted tumors. Initial studies in adults employed both a continuous infusion schedule and a daily bolus x 5 schedule. Myelotoxicity, especially neutropenia, was dose-limiting, with excessive myelotoxicity seen on the daily bolus x 5 at 72 mg/M2/day. Since short infusions may be administered in Ringer's lactate rather than either dimethylsulfoxide or dimethylacetamide required for continuous infusion, this study examined a daily x 5 schedule in children with refractory solid tumors. The initial dosage was 30 mg/M2/day, 80% of the maximum tolerated dosage in adults, with subsequent 30% dosage escalations. A total of 18 patients were enrolled, with a wide spectrum of pediatric solid tumors. Myelosuppression was the only significant toxicity, and was excessive at 78 mg/M2/day. Therefore, on this bolus regimen, 65 mg/M2/day for 5 days was the maximum tolerated dosage. One patient with medulloblastoma had stable disease for 65 days. No other responses were seen.
Bernstein
M L
ML
Montreal Children's Hospital, McGill University, Quebec, Canada.
Whitehead
V M
VM
Grier
H
H
Dubowy
R
R
Land
V
V
Devine
S
S
Murphy
S
S
Kung
F
F
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use* / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; C022121:fazarabine; D001374:Azacitidine