Isolated hyperthermic perfusion with mitoxantrone of melphalan in malignant melanoma of the limb

Melphalan administered by isolated hyperthermic perfusion of the affected limb is an accepted treatment for malignant melanoma of the extremities. In contrast, pharmacologic and phase I studies suggest that, because of its high uptake, mitoxantrone may give even better local control, but data on survival, onset of metastases, and local and systemic toxicities have not yet been reported.

A matched-pairs comparison was performed to examine differences in the tolerability and effectiveness of isolated hyperthermic extremity perfusion with mitoxantrone (n = 44) and melphalan (n = 44) in high risk and locoregionally (P < 0.41) metastatic malignant melanoma. Criteria evaluated were local and systemic complications, and recurrence-free and overall survival.

Local complications, such as delayed wound healing, were more frequent in the mitoxantrone (27.9%) than in the melphalan group (9.8%) (P < 0.05). Systemic toxicity, in particular bone marrow toxicity, was also more severe with mitoxantrone (78.6% versus 15.4%, P < 0.001). Hepatotoxic effects were more frequent among patients in the melphalan group who were older and has lower tissue perfusion temperatures (P < 0.05). There was no difference between the two groups in overall or recurrence-free survival (P < 0.41).

Local and systemic toxicity seem to be higher with mitoxantrone. Survival rates were similar with both drugs. The data obtained suggest a randomized phase II study with an appropriate number of patients.