A phase I trial of fazarabine in refractory pediatric solid tumors : a pediatric oncology group study

• Published in: Investigational new drugs 1993-12, Vol.11 (4), p.309-312
• Main Authors: BERNSTEIN, M. L, WHITEHEAD, V. M, GRIER, H, DUBOWY, R, LAND, V, DEVINE, S, MURPHY, S, FAITH KUNG
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Azacitidine - administration & dosage; Azacitidine - adverse effects; Azacitidine - therapeutic use; Biological and medical sciences; Chemotherapy; Child; Child, Preschool; Drug Administration Schedule; Humans; Medical sciences; Neoplasms - drug therapy; Pharmacology. Drug treatments
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/BF00874429

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.