Regional isolated limb perfusion of melanoma intransit metastases using mechlorethamine (nitrogen mustard)

Forty-two patients with intransit metastases of melanoma in a limb were treated by isolated regional perfusion chemotherapy using mechlorethamine (nitrogen mustard). Group 1 (n = 12) underwent treatment at low dose, less than 0.35 mg/kg, or low temperature, less than 38 degrees C. Group 2 (n = 30) received higher doses, 0.35 to 0.6 mg/kg, plus heat at 38 degrees C to 41 degrees C. No patient had evidence of disease outside the limb at the time of perfusion. The median follow-up time was 48 months (range, 1 to 9 years). Of the 42 patients, 29 had measurable lesions that responded as follows: group 1, complete response (CR) in two of ten and partial response (PR) in none; group 2, CR in six of 19 and PR in six of 19. The combined CR and PR rate of 12 of 19 in group 2 was significantly higher than that of group 1 (P less than .05). CR lasted only 2 months in the two patients of group 1, but persisted in the six patients of Group 2, four of whom are still alive free of disease at 16, 21, 33, and 40 months. Relapse-free control of disease in the limb was achieved in 36% of the patients in group 2 at 24 months, compared with 0% in group 1 (P less than .05). An overall survival of 74% at 48 months was observed in group 2, significantly higher than that of 64% for group 1 (P less than .05). The status of the regional lymph nodes (RLN) and the number of metastases did not affect tumor response. However, 77% of RLN-negative patients survived 48 months, in contrast to only 38% of RLN-positive patients (P less than .05). One patient died postoperatively of myocardial infarction. No serious systemic toxicity developed. Two patients who underwent repeat salvage perfusions developed a reversible peripheral neuropathy in the limb. Limb function was good after treatment, and dramatically improved in patients who had advanced satellitosis that responded to treatment. These results suggest that heated limb perfusion using mechlorethamine at an adequate dose can offer long-term control of intransit metastases in approximately one third of these patients, with preservation of good limb function and possible prolongation of survival.