Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.

Abstract

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...

Noncardiogenic Pulmonary Edema: An Unusual and Serious Complication of Anticancer Therapy

“…This biological response modifier is currently employed in the management of metastatic melanoma and renal cell carcinoma, alone or in combination with chemotherapy or biotherapy [18][19][20][21].…”

Biochemotherapy for the Treatment of Metastatic Malignant Melanoma: A Clinical Practice Guideline

“…Only two trials reported statistically significant response rates favouring treatment with biochemotherapy 8,12 ; five trials failed to detect any significant differences. None of the nine trials detected a statistically significant survival improvement with biochemotherapy.…”

Dacarbazine and interferon α with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG)

“…The cumulative dose of IL-2 in our study (31.5 MIU/m 2 ) is low compared to high-dose schedules used in other trials Legha et al, 1998;Richards et al, 1999). Furthermore, we used an IL-2 administration scheme adapted from the 'decrescendo schedule' introduced by Keilholz and co-workers (Keilholz et al, 1997). In the US-trials continuous infusions with constant doses of IL-2 were preferred Richards et al, 1999;Rosenberg et al, 1999).…”