Phase I clinical and pharmacokinetic study of bisantrene in refractory pediatric solid tumors.
Fourteen patients with pediatric malignant solid tumors, median age 15 years, received 22 courses of bisantrene in a Phase I study. Dosage escalations ranged from 10 to 120 mg/m2 daily for 5 consecutive days. Toxicity included myelosuppression and phlebitis. A sensitive (detection limit of 2 ng/ml) and specific HPLC method was developed to quantitate bisantrene in patient's plasma and urine. Peak plasma concentrations at the end of 60 minute infusions ranged from 568 ng/ml at 10 mg/m2 to 6800 ng/ml at the 100 mg/m2 dosage. The elimination half life (T 1/2 beta) averaged about 10 hours but increased to 20 hours in a patient with liver disease. Only 2.4 - 10% of the bisantrene dose was eliminated in the urine suggesting that the liver may be the major route of elimination for this antineoplastic anthracene derivative.
D000293:Adolescent; D000328:Adult; D000873:Anthracenes / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000188:drug therapy*
D000873:Anthracenes; C031404:bisantrene