Extravasation of dactinomycin, vincristine, and cisplatin: studies in an animal model

Extravasation of some cytotoxic drugs results in chemical cellulitis. Management of suspected extravasation has been empiric and difficult to evaluate clinically. We investigated dactinomycin, vincristine, and cisplatin by means of intradermal injections in Balb-c mice. Reproducible skin lesions with concentric areas of induration, erythema, and ulceration developed in a time- and dose-dependent fashion following injection of dactinomycin. Vincristine caused no lesions following initial intradermal administration, but repeat injection 7 days later was followed by a diffuse punctate ulcerative lesion suggesting a hypersensitivity reaction. Three concentrations (1.0, 0.1, and 0.01 mg/ml) of cisplatin elicited cellulitis following initial injection, but there was no correlation between lesion size and dose. Injection of saline, hydrocortisone, ascorbic acid, sodium thiosulfate, buffered DNA solution, and beta adrenergic agonists and antagonists after the injection of dactinomycin failed to prevent development of lesions. Heat application was also ineffective; however, local cold application prevented or markedly reduced reactions to dactinomycin. We conclude that the intradermal mouse model may be appropriate for the evaluation of the three drugs studied and that cold application is the best antidote among those tested for dactinomycin-induced ulceration in this model.