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Severe hepatic toxicity after treatment with single‐dose dactinomycin and vincristine. A report of the national wilms' tumor study
Author(s) -
Green Daniel M.,
Finklestein Jerry Z.,
Norkool Patricia,
J. D'Angio Giulio
Publication year - 1988
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19880715)62:2<270::aid-cncr2820620208>3.0.co;2-b
Subject(s) - medicine , toxicity , dactinomycin , wilms' tumor , vincristine , clinical trial , microgram , pharmacology , chemotherapy , route of administration , surgery , in vitro , biology , biochemistry , cycloheximide , microbiology and biotechnology , protein biosynthesis , cyclophosphamide
Dactinomycin is an antitumor antibiotic with known activity against many pediatric solid tumors. Administration of dactinomycin using a single‐dose schedule was incorporated into the design of the National Wilms' Tumor Study 4 (NWTS‐4). This was done to determine whether laboratory and preliminary clinical data, suggesting that such a schedule was associated with increased antitumor effect and/or decreased normal tissue toxicity, could be validated in a large clinical trial. Five patients treated with regimens EE‐4 or K‐4, regimens that included single‐dose dactinomycin and no abdominal irradiation, experienced severe hepatic toxicity. The clinical courses of these patients suggested that multiple factors, including the administration of other hepatotoxic agents, contributed to the toxicity observed. The study has been modified by decreasing the dose of dactinomycin from 60 μ/kg to 45 μ/kg. Further evaluation of other potential contributing factors, such as the use of halogenated hydrocarbon inhalational anesthetic agents, is needed.