A randomized prospective clinical trial of adjuvant C. parvum immunotherapy in 260 patients with clinically localized melanoma (Stage I): Prognostic factors analysis and preliminary results of immunotherayp

A total of 260 patients with clinically localized melanoma (Stage I) from 18 medical institutions in the Southeastern Cancer Study Group were randomized to receive either surgical treatment alone, or surgery plus Corynebacterium parvum immunotherapy. A multivariant analysis (Cox regression model) of nine prognostic factors was performed on 110 patients with a minimum of two years follow‐up. The dominant prognostic variables were thickness (P = 0.0007) and anatomic location of the melanoma (trunk versus other, P = 0.015). Disease‐free survival curves were then calculated for 204 surgically evaluable patients. Overall, there was no significant difference in three‐year survival for the two‐treatment arms, which was 81% for the adjuvant immunotherapy group compared to 67% for the surgical control group (P = 0.10). The median follow‐up period was 24 months (range, 1‐60 months). However, when the data was subgrouped by tumor thickness, an apparent benefit of immunotherapy was observed in 49 patients with melanomas greater than 3 mm in thickness. Only five of 23 such patients relapsed after receiving C. parvum. Their three‐year disease‐free survival was 73%. In contrast, 13 of 26 patients who did not receive immunotherapy have relapsed so far and their three‐year disease‐free survival was only 33% (P = 0.01). In the 175 patients with melanomas less than 3 mm in thickness, both treatment arms had identical three‐year disease‐free survival rates of 83%. No significant differences between the treatment arms were observed using other prognostic variables, including the level of invasion. Toxicity to C. parvum injections was minimal in most patients. It is concluded that a prognostic factors analysis is critically important in adjunctive trials of melanoma to determine which dominant variables should be used for analyzing patient subgroups; that C. parvum immunotherapy appears to be associated with an improved disease‐free survival rate in the subgroup of patients with melanomas >3 mm thickness (this early encouraging data must still be confirmed with continued patients accrual and a longer observation period); and that patients with melanomas less than 3 mm thick have a relatively favorable prognosis after appropriate surgical treatment, and immunotherapy does not improve their survival rates.