Current clinical relevance of immunotherapy in metastatic renal cell cancer

Existing compilations of data recorded in clinical trials involving cytokines as single compounds and in combination with each other and with cellular immuno-effectors or chemotherapeutic agents are analyzed. Antitumor activity for interferon alpha (IFN-α) and for interleukin-2 (IL-2) could be established at 14.5% and 13.7%, respectively, when used in single-agent regimens with considerable toxicity for IL-2 at high, intravenous doses. When IL-2 is combined with cellular effectors, these side effects together with the problems associated with the complexity of culture techniques when adding LAK (lymphokine-activated killer) cells or CTILs (cytotoxic tumor-infiltrating lymphocytes) impact unfavorably on future clinical application, and this combination must be considered investigational. IFN-α or IL-2 coupled with a chemotherapeutic agent only exhibited a limited advantage over single cytokine administration. The most promising combination seems to be IFN-α combined with IL-2, giving improved prospects for nearly 30% of the patients with metastatic renal cell cancer (RCC), simultaneously allowing for significant reduction of toxicity and for an outpatient treatment. A precise assessment of the underlying immunologic mechanisms is needed, as are controlled prospective and randomized trials comparing the various cytokines with each other and with conventional approaches in single and combination regimens with the ultimate purpose of defining the role of biotherapy within a clinical strategy for metastatic RCC before it can be considered a standard treatment modality.