Improvement in systemic antitumor responses is needed before this approach can prove useful as adjunctive treatment following induction chemotherapy in patients with minimal residual disease.

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Purpose: The combination of interferon alfa-2a (IFNa) and high-dose interleukin-2 (IL-2) is active in met astatic melanoma. The addition of cisplatin (CDDP) has resulted in response rates greater than 50%. This study was performed to determine whether the addition of CDDP to a cytokine treatment regimen with IFNa and high-dose IL-2 influences survival of patients with meta static melanoma.Patients and Methods: Patients with advanced metastatic melanoma were randomly assigned to receive treatment with IFNa; 10 x 10 6 U/m2 subcutaneously on days 1 through 5 and a high-dose intravenous decre scendo regimen of IL-2 on days 3 through 8 (18 mlU/ m2/6 hours, 18 mlU/m2/12 hours, 18 mlU/m2/24 hours, and 4.5 mlU/m2/24 hours x 3) without (arm A) or with (arm D) CDDP 100 mg/m2 on day 1. Treatment cycles were repeated every 28 days to a maximum of four cy cles.T HERE IS NO STANDARD treatment for advanced metastatic melanoma. With dacarbazine as a single agent, an approximately 15% objective remission rate can be achieved with a duration of 4 to 6 months.1,2 Combination chemotherapy may increase response rates up to 40%, but without an impact on survival.1,3 The activity of interleukin-2 (IL-2) has been extensively tested during the past decade.4'7 Up to 20% of patients have experienced tumor responses with IL-2 administered in high-dose regimens, and some long-term survivors have been reported in most trials. Interferon alfa (IFNa) is also an active agent in melanoma.8 Twenty percent to 40% of patients achieve objective remissions with the combina tion of IL-2 and IFNa:.9*12The addition of dacarbazine to IL-2 in phase II trials resulted in response rates similar to those achieved with IL-2 treatment alone.13'15 More recently, several singleinstitution trials have investigated the combination of var ious cytotoxic agents with IFNa and high-dose IL-216-18 and a multicenter phase II trial that combined cisplatin (CDDP), dacarbazine, and tamoxifen with high-dose IL-2 has been performed by the Cytokine Working Group.19 Sixteen percent to 56% objective response rates were achieved with these combinations that involved two to six agents. When the three agents CDDP, IFNa, and highdose IL-2 were part of the treatment regimen, the response Results: One hundred thirty-eight patients with ad vanced metastatic melanoma, of whom 87% had visceral metastases, were accrued for the trial. Both regimens w ere feasible in a multicenter setting. The objective re sponse rate w as 18% without and 33% with CDDP (P = .04). The progression-free survival w as 53 days without and 92 days with CDDP (P = .02, Wilcoxon; P = .09, logrank). There w as no statistically significant difference in survival between treatment arms, with a median overall survival duration for all patients of 9 months.Conclusion: The addition of CDDP to cytokine treatment with IFNa and IL-2 does not influence survival of patients with advanced metastatic melanoma, despite a significant increase in response rate and progressionfree survival.J Clin Oncol 15:2579-2588. © 1997 by Ameri...

Serum LDH, metastatic site, and performance status are useful stratification factors for randomized trials in metastatic melanoma. The improved long-term survival rates observed in melanoma patients treated with IL-2/IFNalpha-containing regimens are notable in contrast to the reported 5-year survival rates of 2% to 6% achieved with chemotherapy, but because selection bias cannot be ruled out, the impact of IL-2, as well as all other components of the treatment regimens, on survival needs to be confirmed in prospective randomized trials.

In this phase II to III study, AT resulted in a significantly longer TTP and OS and a higher objective ORR than FAC. First-line AT is a valid treatment option for patients with MBC.