Prophylactic isolated limb perfusion for localized, high-risk limb melanoma:: Results of a multicenter randomized phase III trial

Purpose: Patients with primary cutaneous melanoma greater than or equal to 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. Patients and Methods: A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia, Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness greater than or equal to 3 mm. Results: Median follow-vp duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND), The impact of ILP was clearly on the occurrence - as first site of progression - of in transit metastases (ITM), which were reduced from 6.6% to 3,3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%, There was no benefit from lip in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP, Conclusion: prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma, J Clin Oncol 16:2906-2912. (C) 1998 by American Society of Clinical Oncology.