TREATMENT OF IN-TRANSIT METASTASES FROM CUTANEOUS MELANOMA BY ISOLATION PERFUSION WITH TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA), MELPHALAN AND INTERFERON-GAMMA (IFN-GAMMA) DOSE-FINDING EXPERIENCE AT THE NATIONAL-CANCER-INSTITUTE-OF-MILAN

From December 1991 to July 1993, 22 consecutive patients with grade II IA-IIIAB melanoma underwent isolation perfusion with TNF-alpha (0.5-4 mg), melphalan (10 mg/l perfused limb) and, in the first 12 cases, IFN -gamma (1.5 x 10(6) U). The first series of 12 patients received a tot al dosage TNF-alpha of 2-4 mg, and the second series of 10 cases recei ved an escalating dosage of TNF-alpha (1.5-1.0-0.5 mg) and no IFN-gamm a before or during surgery. The perfusion lasted 90 min and was conduc ted in mild hyperthermia (39-39.5-degrees-C muscle temperature). The r esults of the first series included seven patients in complete remissi on, four with stable disease and one case not evaluable for local toxi city. Fifty per cent of cases developed a regional relapse from 3 to 4 months after surgery. Presently with a median follow up of 10 months, five patients of this group have no evidence of disease, four are ali ve with disease, two died from melanoma and one died of complications likely due to treatment (multi-organ failure syndrome). In the second series, the immediate responses included seven patients in complete re mission and three in partial remission; with a median follow up of 3 m onths, two patients developed a regional relapse, respectively, 3 and 5 months after surgery. So far our experience of perfusion with TNF-al pha has not reproduced the data reported by other investigators. Furth er clinical and biological findings and a longer follow-up period are needed to draw any conclusion, and a decreasing TNF-alpha dose should be carefully evaluated.