A Randomized Trial of Adjuvant Chemotherapy and Immunotherapy in Cutaneous Melanoma

In a randomized trial of adjuvant chemotherapy, immunotherapy, or immunochemotherapy, 761 evaluable patients with pathological Stage II cutaneous melanoma anywhere on the body or with pathological Stage I melanoma of the trunk (Clark's level 3 to 5) were studied by the World Health Organization International Melanoma Group. Wide local excision and excisional regional lymphadenectomy alone were performed in 185 patients and the results were compared with those of surgery plus chemotherapy with dacarbazine (in 192 patients), surgery plus immunotherapy with bacille Calmette–Guérin vaccine (in 203), and surgery plus chemotherapy combined with immunotherapy (in 181). The rates of disease-free survival and overall survival at 36 months were 30.4±8.3 per cent (mean ±S.E.) and 41.6±10.0 per cent, respectively, after surgical treatment alone; 37.2±7.9 per cent and 46.5±8.3 per cent after surgery plus chemotherapy; 34.8±7.9 per cent and 48.7±8.7 per cent after surgery plus immunotherapy; and 33.6±7.9 per cent and 50.0±8.8 per cent after surgery plus a combination of chemotherapy and immunotherapy. None of the differences between groups was significant, and thus no effect of adjuvant therapy could be demonstrated in this study. (N Engl J Med. 1982; 307:913–6.) The rationale for combining surgery and chemotherapy in the treatment of melanoma was developed from new concepts derived from studies in animals, which showed that the efficacy of chemotherapy is inversely related to the total tumor-cell burden. Chemotherapy was therefore considered more effective when given immediately after surgery rather than at the time of the appearance of clinical metastases. 1 , 2 In experimental models bacille Calmette–Guérin (BCG) vaccine was also useful as adjuvant therapy, in that it prevented the growth of tumor cells, reduced the volume of metastatic spread, and prolonged survival when given immediately after surgery. 3 4 5 Although the first clinical trials . . .