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: M L Bernstein, V M Whitehead, H Grier, R Dubowy, V Land, S Devine, S Murphy, F Kung
• Journal: Investigational new drugs (Invest New Drugs) Vol. 11 Issue 4 Pg. 309-12 (Nov 1993) ISSN: 0167-6997 [Print] United States
• PMID: 7512539 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• fazarabine
• Azacitidine

Topics

• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Azacitidine (administration & dosage, adverse effects, therapeutic use)
• Child
• Child, Preschool
• Drug Administration Schedule
• Humans
• Neoplasms (drug therapy)