Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies.
Cytosine arabinoside (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m2 as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9-12 and 21-24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m2 X 2 doses of ara-C and 50 mg/m2 of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy; D003561:Cytarabine / Q000008:administration & dosage; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008875:Middle Aged
D003561:Cytarabine; D005047:Etoposide