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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.
Insights
Cisplatin, L-PAM, and mitoxantrone chemotherapy drugs were evaluated for skin damage potential. Studies found these anticancer agents are not vesicants at clinical doses.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Cisplatin and L-PAM are DNA-crosslinking anticancer agents.
- Mitoxantrone is an anthracene-based DNA intercalator used in cancer treatment.
- Systematic study of vesicant potential for these agents was lacking.
Purpose of the Study:
- To evaluate the vesicant potential of cisplatin, L-PAM, and mitoxantrone.
- To determine if these anticancer drugs cause skin necrosis at clinical doses.
Main Methods:
- Dehaired BALB/c mice received intradermal injections of cisplatin, L-PAM, or mitoxantrone.
- Doses administered were equivalent to human clinical doses.
- Skin sites were monitored for necrosis and ulceration.
Main Results:
- Cisplatin (up to 150 mg/m2) and L-PAM (up to 71 mg/m2) did not cause skin necrosis.
- Mitoxantrone (up to 14 mg/m2) was not ulcerogenic, but caused temporary blue skin discoloration.
- The L-PAM solvent alone was ulcerogenic when undiluted.
Conclusions:
- Cisplatin, L-PAM, and mitoxantrone are not vesicants at clinically relevant doses.
- The solvent for L-PAM may possess ulcerogenic properties.
- Further investigation into drug-specific tissue reactions is warranted.