Disseminated malignant melanoma and recombinant interferon: Analysis of seven consecutive phase II investigations

We have performed seven phase II trials with recombinant interferons (IFN) involving 191 patients with biopsyproved, measurable disseminated malignant melanoma. The regimens and numbers of patients have included IFN-α2A, 50 × 10⁶ U/m² subcutaneous (SQ) TIW (regimen A, 31 patients); IFN-α2A, 12 × 10⁶ U/m² SQ TIW (regimen B, 30 patients); IFN-α2A with cimetidine as an immunorestorative agent (regimen C, 35 patients); IFN-γ (regimen E, 29 patients); IFN-α2A with IFN-γ (Regimen E, 20 patients); IFN-α2A with bis-chloroethylnitrosourea (BCNU) (regimen F, 30 patients); and IFN-α2A with the biochemical modulator, difluoromethylornithine (DFMO) (regimen G, 16 patients). The objective regression rates were as follows: A, 23%; B, 20%; C, 23%; D, 10%; E, 5%; F, 7%; G, 0%. Despite the higher response rate from regimen A, there appeared to be no survival advantage from any of these programs. The median time to progression was 1 month with a median survival time of 6 months. Most regressions involved soft tissue disease, were partial, and occurred within 2-3 months of treatment. Four patients received IFN for approximately 6 months and have manifested extraordinarily durable regressions of > 4+ years. The α-regimens produced a flu-type illness and anorexia which were dose-related. Leukopenia was most noteworthy with regimens containing γ-interferon. Ongoing trials involving alternative and improved immune-related modalities are awaited with keen interest.