Adjuvant Treatment in Stage I and II Malignant Melanoma: A Randomized Trial between Chemoimmunotherapy and Immunotherapy

Abstract

A randomized trial comparing chemoimmunotherapy (bacillus Calmette-Guérin + chemotherapy) and immunotherapy (bacillus Calmette-Guérin alone) was carried out in high-risk stage I and II malignant melanoma patients. Eighty-two evaluable patients were included. The follow-up median duration was 11 years. Recurrent melanoma developed in 28 patients (34%). The overall survival rate was 76% at 5 years and 65% at 10 years. There were no statistical differences in survival probability or disease-free survival (DFS) probability between the two treatment groups. Survival and DFS were also analyzed in relation to various prognostic factors. Statistically significant differences were only seen in a subset of 33 patients with lower limb malignant melanoma, the prognosis being better for the chemoimmunotherapy group in this location. Because of the small number of patients in each group, a week positive effect of either of these two treatments cannot be ruled out. Chemoimmunotherapy only seems to improve the prognosis of stage I or II malignant melanoma of the legs.

A treatment for metastatic melanoma?

“…Multiagent cytotoxic therapy is similarly unhelpful in the adjuvant setting. Other trials of multiagent chemotherapy using nitrosoureas, dactinomycin and vincristine present contrary results (1983, Castel et al, 1991, McClay et al, 2000, Pawlik and Sondak, 2003, Wood et al, 1978).…”

Current state of treatment for primary cutaneous melanoma

“…A trial using BCNU, dactinomycin, and vincristine [58] and a small trial of DTIC, CCNU, and vincristine [59] both suggested a benefit for multiagent chemotherapy, while two other trials did not [60,61]. Several small trials have also explored postoperative adjuvant therapy with DTIC plus BCG, with [55,62] or without a no-treatment arm [63][64][65][66][67]. DTIC plus BCG does not appear to have any efficacy in the adjuvant setting, which is hardly surprising in view of the lack of activity of the individual agents and the absence of any suggestion of synergy between them.…”

“…Early trials utilized low-or intermediate-dose regimens, and while there was a suggestion of some effectiveness [92,93], re-analysis and additional trials have demonstrated no benefit to survival [94,95]. Although there was no overall survival advantage, the disease-free survival advantage to low-dose IFN seen in the French and Austrian trials has led to its approval in Europe for thick primary melanomas [66,67] Unfortunately, the recently published results of the AIM-HIGH study in the United Kingdom of low-dose extendedduration IFN-α2a demonstrated no clear differences between IFN and observation in either overall or relapsefree survival for any subset of patients [98].…”