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PTG, a new antineoplastic epipodophyllotoxin
Author(s) -
Creaven Patrick J.,
Allen Larry M.
Publication year - 1975
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1975182227
Subject(s) - leukopenia , medicine , pharmacokinetics , vinca , urine , metabolite , toxicity , body surface area , urology , gastroenterology , pharmacology
The pharmacology of 4'‐demethylepipodophyllotoxin 9‐(4, 6‐0‐thenylidene‐β‐Dglucopyranoside) PTG, a new anticancer drug, is reported. Six patients with advanced cancer were treated witli PTG (67 mg/m 2 of body surface area intravenously) specifically labeled with tritium as the first dose of a weekly × 6 course. Recovery of drug in the urine was 44.49 ± 8.2% ofthe administered dose in 72 hr, of which 78.7 ± 5.1% was metabolite. Recovery in thefeces was 0 to 10.05% in 4 patients. Plasma decay fitted the equation Cp = Ae ‐αt + Be ‐βt + Ce ‐yt by nonlinear least‐squares regression. Mean values for the parameters (after infusion) were A 14.3 ± 5.5, B 9.66 ± 3.98, C 2.44 ± 1.33 µg/ml; α 2.05 ± 1.25, β0.26 ± 0.15, σ 0.038 ± 0.016 hr ‐1 , Levels of drug in the cerebrospinal fluid (CSF) were <1 % of plasma levels in 3 patients at 24 hr after treatment and 27% in 1 patient who had had brain surgery and brain radiotherapy. Four of 4 patients considered evaluable for toxicity (>2 consecutive weekly doses) developed leukopenia (WBC <5,000/mm 3 ). Mean nadir of WBC was 3,600/mm 3 . The most marked leukopenia (WBC, 2,300/mm 3 ) was seen in the patient with the longest terminal phase plasma half‐life (38.5 hr). Two of 5 patients evaluable for response received clinical benefit (1 laryngeal carcinoma, 1 histiocytic lymphoma). It is concluded that PTG has a long terminal phase half‐life (11‐38.5 hr), is largely metabolized, and does not penetrate the normal blood‐brain barrier.