title: A phase I trial of fazarabine in refractory pediatric solid tumors. A Pediatric Oncology Group study.
abstract: 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.
authors.affiliation: Montreal Children's Hospital, McGill University, Quebec, Canada.
authors.forename: M L
authors.initials: ML
authors.lastname: Bernstein
authors.forename: V M
authors.initials: VM
authors.lastname: Whitehead
authors.forename: H
authors.initials: H
authors.lastname: Grier
authors.forename: R
authors.initials: R
authors.lastname: Dubowy
authors.forename: V
authors.initials: V
authors.lastname: Land
authors.forename: S
authors.initials: S
authors.lastname: Devine
authors.forename: S
authors.initials: S
authors.lastname: Murphy
authors.forename: F
authors.initials: F
authors.lastname: Kung
mesh_terms: 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*
chemical_list: D000970:Antineoplastic Agents; C022121:fazarabine; D001374:Azacitidine