Intradermal carboplatin and ifosfamide extravasation in the mouse.

Abstract

Carboplatin and ifosfamide are new antineoplastic agents with vesicant properties that have not been determined. Vesicant activity was investigated in Balb-c mice by administering carboplatin or ifosfamide intradermally in clinically relevant concentrations. Carboplatin concentrations tested were 15, 10, and 1 mg/ml; those of ifosfamide were 50, 20, and 1 mg/ml. Five female mice were tested with each concentration; and five animals were used as controls and received only saline. Carboplatin concentrations of 15 mg/ml and 10 mg/ml produced mean peak ulcer areas of 10 square millimeters (mm2) and 21 mm2 within 2-3 days of injection, respectively. The 1 mg/ml carboplatin injection was not associated with any ulcer formation. Ifosfamide at 50 mg/ml induced skin ulcerations in four of five mice, with maximal effect (19.6 mm2) by 1-2 days. Lower concentrations of ifosfamide produced no ulcerations. All ulcerative lesions healed completely within 21 days. These results suggest that extravasation of carboplatin at concentrations of greater than or equal to 10 mg/ml or ifosfamide at concentrations of greater than or equal to 50 mg/ml is likely to cause ulcers in humans.