The role of interferon and interleukin-2 in the immunotherapeutic approach to renal cell carcinoma.

Approximately 24,000 cases of renal cell carcinoma are expected in the United States in 1990. Although approximately 50% of patients with local disease are cured by surgery, in patients with metastatic disease the median survival is only approximately 10 months. Neither chemotherapy nor radiation therapy has been shown to be effective against metastatic renal cell carcinoma. Immunotherapy has come to the forefront of clinical research for the treatment of metastatic renal cell carcinoma. In the past decade, the development of recombinant DNA techniques has enabled the production of large quantities of biologic response modifiers such as the interferons and interleukins. Following initial reports in 1983 by the University of California-Los Angeles (UCLA) group and the investigators at M. D. Anderson Hospital, in Houston, TX, numerous trials have demonstrated a reproducible objective response rate to interferon of 15% to 20%. These responses are independent of the interferon preparation used, and optimal dosage/schedule has not been determined. In general, responses have been correlated with the following patient factors: previous nephrectomy, good performance status, a long disease-free interval, and lung-predominant disease. Median response durations of from 8 to 10 months can be expected. The addition of vinblastine, gamma-interferon, or aspirin has not improved the therapeutic index. Interleukin-2 therapy has produced encouraging results in 10% to 15% of patients. Although high-dose therapy is associated with substantive side effects, a small cohort of patients have been in continuous remission for extended periods of time, raising the possibility of "true" complete remissions of clinical significance. Recent trials, including our trials at UCLA, have combined the interleukins and interferons in this patient population. This combination has a sound scientific basis and the results are encouraging, especially when the toxicity profile is considered. Most patients receive these combinations as outpatients and have not required hospitalization nor suffered the toxicities of the high-dosage regimens. Complete pathologic remissions have been observed using this lower dosage, outpatient schedule. Clinical trials suggest that interferon and interleukin-2 may have an expanding role in metastatic kidney cancer both as single agents and in combination outpatient biologic therapy. The future clinical trials of kidney cancer will continue to incorporate these biologic response modifiers into the therapeutic strategies of the 1990s.