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Cytokines in Metastatic Renal Cell Carcinoma: Is It Useful to Switch to Interleukin-2 or Interferon After Failure of a First Treatment?

From the Institut Gustave Roussy, Villejuif; Centre Claudius Régaud, Toulouse; Centre Léon Bérard, Lyon; Centre René Gauducheau, Nantes; Institut Bergonié, Bordeaux; Centre Val d'Aurelle, Montpellier; Centre Oscar Lambret, Lille; CHU, Montpellier; Institut Paoli Calmettes, Marseille; and CHU, Strasbourg, France.

Address reprint requests to Bernard Escudier, MD, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France; email escudier{at}igr.fr

PURPOSE: Interleukin-2 (IL-2) and interferon alfa-2a (IFN2a) have some antitumor activity in metastatic renal cell carcinoma either alone or in combination. To determine whether either of these cytokines might be efficient after failure of the other, we analyzed a series of patients treated with either IL-2 or IFN2a as second-line treatment after failure of the other cytokine.

PATIENTS AND METHODS: We recently performed a large multicenter study to determine the respective efficacy of IL-2, IFN2a, or combined treatment in renal cell carcinoma. In this study, patients who progressed on the single-arm treatment could receive the other cytokine in a cross-over trial. IL-2 was administered as a continuous intravenous infusion for 5 days (18 x 10⁶ IU/m²/d), and IFN2a was administered three times weekly at 18 x 10⁶ IU.

RESULTS: A total of 113 patients with progressive disease after first-line treatment received either IFN2a (n = 48) or IL-2 (n = 65). Toxicity during second-line treatment was similar to that observed during first-line treatment. Only four partial responses were observed (one with IFN2a and three with IL-2). All partial responders had a performance status of 0 and lung metastases. Moreover, three of these four patients had stable disease or had responded to first-line therapy. Only one patient with confirmed disease progression after receiving IL-2 subsequently responded to IFN2a.

CONCLUSION: Cross-over after failure of IL-2 or IFN2a is poorly efficient in metastatic renal cell carcinoma, especially when progression has been clearly documented.

The Groupe Français d'Immunothérapie is part of the Fédération Nationale des Centres de Lutte Contre le Cancer; the names of additional investigators are listed in the Appendix.

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