Natural history and therapy of metastatic renal cell carcinoma: the role of interleukin-2.

BACKGROUND: Despite significant advances in understanding the biology of renal cell carcinoma (RCC) during the past decade, metastatic disease remains nearly incurable and a major medical challenge. Because RCC is known to be immunogenic, immunotherapeutic agents such as recombinant human interleukin-2 (rIL-2) and interferon-alpha (IFN-alpha) have represented encouraging treatment modalities.
METHODS: A review of the natural history of and therapeutic approaches to RCC was examined. Studies involving rIL-2 alone and in combination with other adjuvant therapies were critically evaluated.
RESULTS: Overall response rates for metastatic RCC patients treated with rIL-2 were similar (i.e., in the range of 15-20%), regardless of whether rIL-2 was administered as monotherapy or in combination with IFN-alpha. Recombinant IL-2 monotherapy response rates were similar to those of IFN-alpha, but with an increased frequency of complete responses and enhanced response duration. Subcutaneous administration generally resulted in lower toxicity than intravenous administration. The roles of chemotherapy or adoptive immunotherapy in combination with rIL-2 and IFN-alpha therapy remain unclear and require further study. The importance of patient performance status as a predictor of response and survival in rIL-2 therapy was demonstrated.
CONCLUSIONS: The use of rIL-2 with or without IFN-alpha may represent the most useful therapeutic approach currently available for patients with good performance status. In patients with borderline performance status or severe comorbid disease, therapeutic approaches depend on patient factors and outcome expectation and may involve cytokine therapy. However, regardless of performance status, palliative measures and/or observation are important choices, because the majority of patients with metastatic RCC are incurable.