title: Lack of experimental vesicant activity for the anticancer agents cisplatin, melphalan, and mitoxantrone.
abstract: Cisplatin and L-PAM are DNA-crosslinking anticancer agents which have not been systematically studied for vesicant potential. Mitoxantrone is a new active anthracene-based, DNA intercalator which is undergoing widespread clinical testing for antitumor efficacy in man. These three agents were tested for vesicant activity in dehaired BALB/c mice given ID injections equivalent to human clinical doses. Neither cisplatin (up to 150 mg/m2) nor L-PAM (up to 71 mg/m2) produced any skin necrosis in the mice. The L-PAM solvent (acid/alcohol in propylene glycol) was ulcerogenic if injected undiluted. Mitoxantrone (up to 14 mg/m2) was not ulcerogenic in the mice, although the skin site retained a blue drug discoloration for several weeks. It is concluded that in clinically relevant doses, cisplatin, L-PAM, and mitoxantrone are not vesicants.
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D005260:Female; D007271:Injections, Intradermal; D007509:Irritants; D008558:Melphalan / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008942:Mitoxantrone; D012883:Skin Ulcer / Q000139:chemically induced*
chemical_list: D000880:Anthraquinones; D007509:Irritants; D008942:Mitoxantrone; D002945:Cisplatin; D008558:Melphalan