The Role of Cytokine Therapy in Metastatic Renal Cell Cancer

ObjectivesTreatment of metastatic renal cell cancer (mRCC) is rapidly evolving since evidence concerning efficacy of novel molecular targeted drugs recently became available. This paper provides a critical overview of the current and future role of cytokine-based immunotherapy in mRCC in light of these new developments.MethodsPublished data from phase 3 studies and meta-analyses were analyzed by means of a systematic literature search in PubMed and Medline databases.ResultsRandomized trials using interferon-α (IFN-α), interleukin-2 (IL-2), and combinations have produced overall response rates of 4–31%. For IFN-α, a modest but significant survival advantage of 2.5 mo over hormonal therapy has been demonstrated. No significant survival advantage was shown for IL-2. High-dose IL-2 may induce complete and durable regression of mRCC in up to 5% of patients, but is characterized by high toxicity. Placebo-controlled prospective studies with these cytokines have not been published. Results from cytokine combination trials are difficult to compare because of differences in administration, dosing, and schedules. No internationally recognized standard immunotherapy treatment protocol could be defined for mRCC. Tyrosine kinase inhibitors achieve objective response or disease stabilization in a higher proportion of patients, but neither cure nor significant survival advantage has been shown for these agents. Combined and sequential treatments with cytokines and targeted agents are being investigated.ConclusionsFor selected patients, first-line cytokine therapy may still be an option in the repertoire of therapies for mRCC. A better knowledge of molecular markers could allow rational use of different therapies in individual patients in the future.