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 biopsy- proved, 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 IFNγ (Regimen E, 20 patients); IFN-α2A with bis-chioroethylnitrosourea (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.