Natural history and therapy of metastatic renal cell carcinoma

The role of interleukin-2

The activity of interleukin-2 was evaluated in a review of the efficacy of immunomodulatory agents in the treatment of patients with metastatic renal cell carcinoma. Cytokine therapy may represent the most useful approach currently available for a subset of patients, but palliative measures, observation, or experimental therapy remain important options due to the nearly incurable nature of the disease.

Abstract

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-α (IFN-α) 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-α. Recombinant IL-2 monotherapy response rates were similar to those of IFN-α, 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-α 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-α 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. Cancer 1997; 80:1198-220. © 1997 American Cancer Society.