Antidote studies of vinorelbine-induced skin ulceration in the mouse

The new cantharanthine-modified vinca alkaloid vinorelbine (Navelbine) was administered intradermally (ID) to dehaired BALB/c mice. Dose-dependent skin lesions were produced over the range 0.01-0.5 mg/mouse, with complete healing after 9-35 days. Local (ID) injections of hydrocortisone and saline were ineffective at blocking vinorelbine-induced skin ulceration. Topical skin heating to 43 degrees C or cooling to 10 degrees C were also ineffective. In contrast, hyaluronidase, 15 Units ID, following vinorelbine significantly reduced skin lesions. These results show that vinorelbine is a vesicant and that inadvertent extravasations may be managed with subcutaneous injection of the spreading factor enzyme, hyaluronidase.