Phase I clinical investigation of fludarabine phosphate by a loading-dose and continuous-infusion schedule.
Fludarabine phosphate was studied in a phase I trial of a loading-dose/continuous-infusion schedule. The schedule was chosen to rapidly achieve and maintain concentrations that have been shown in vitro to achieve maximal inhibition of cell growth. The initial level was a loading dose of 20 mg/m2 followed by a 48-hour continuous iv (CIV) infusion of 30 mg/m2 every 24 hours. For the single-dose escalation, the loading dose was held constant while the CIV dose was increased to 45 mg/m2/24 hours for 48 hours. The dose-limiting toxicity was myelosuppression, especially leukopenia. No other significant toxicity was encountered. The maximum tolerated dose was 20 mg/m2 by iv push followed by a 48-hour CIV infusion of 30 mg/m2/24 hours for 48 hours. The recommended starting dose for phase II trials is 20 mg/m2 by iv push followed by a 48-hour CIV infusion of 30 mg/m2/24 hours. This dose level achieved the target plasma levels in the 2 patients studied.
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001088:Arabinonucleotides / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009420:Nervous System / Q000187:drug effects; D001084:Vidarabine Phosphate / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood
D000964:Antimetabolites, Antineoplastic; D001088:Arabinonucleotides; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate