title: Phase I study of the anthrapyrazole biantrazole: clinical results and pharmacology.
abstract: In a phase I study the anthrapyrazole biantrazole (Warner-Lambert Company) was given to 41 patients with tumour refractory to existing therapy. The drug was given i.v. weekly for 3 weeks, with a 3-week interval between courses. At the 1st week a full pharmacokinetic study was performed, and at weeks 2 and 3, blood samples were taken at 1 and 6 h following treatment to check for drug accumulation. Biantrazole pharmacokinetics were linear with respect to the AUC (r = 0.924) over the full range of doses studied (4-36 mg/m2) but exhibited large inter-patient variations at each dose level. Elimination was triphasic, comprising two rapid early phases and a long terminal half-life (mean, 14.1 +/- 7.8 h). There was no evidence of drug accumulation over the 3-week treatment period. Approximately 12% of the parent drug was excreted unchanged in the urine together with two non-circulating, more water-soluble metabolites. Biantrazole was well tolerated but did cause moderate emesis at doses of greater than 18 mg/m2 and mild alopecia. The dose-limiting side effect was leucopenia, with no other major toxicity being observed. One patient developed biventricular failure that was not clearly related to biantrazole administration. On the present schedule, the recommended dose of biantrazole is 24 mg/m2. No response were seen in this patient population.
authors.affiliation: Medical Oncology Unit, Western General Hospital, Edinburgh, UK.
authors.forename: S G
authors.initials: SG
authors.lastname: Allan
authors.forename: J
authors.initials: J
authors.lastname: Cummings
authors.forename: S
authors.initials: S
authors.lastname: Evans
authors.forename: M
authors.initials: M
authors.lastname: Nicolson
authors.forename: M E
authors.initials: ME
authors.lastname: Stewart
authors.forename: J
authors.initials: J
authors.lastname: Cassidy
authors.forename: M
authors.initials: M
authors.lastname: Soukop
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
authors.forename: J F
authors.initials: JF
authors.lastname: Smyth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D013997:Time Factors
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C055925:anthrapyrazole