Interferon treatment of renal cell carcinoma. Current status and future prospects

Studies with various interferon alpha preparations, including interferons induced in human leukocytes, interferon alfa-N1, interferon alfa-2a, and interferon alfa-2b, have all provided evidence for modest but reproducible antitumor activity in advanced renal cell carcinoma. Review of the data suggests that maximal response rates are achieved when interferon alpha is administered within a fairly restricted range of moderate to high doses, whereas extremely low or extremely high dosage regimens appear less likely to induce therapeutic response. Preliminary evidence suggests that interferons beta and gamma may also induce regression of metastatic renal cell carcinoma. Recent in vitro and animal studies have shown that combinations of interferon gamma with interferon alpha or interferon beta, produce synergistic biologic activities, suggesting that the various interferons may have different pathways of action related to agent-specific cellular receptors. Possible interactions of different interferon species given concurrently to patients with renal cell carcinoma are under investigation, as are combinations of interferon alpha with chemotherapeutic agents. Despite in vitro data suggesting enhanced antiproliferative activity for the combination of interferon alpha and vinblastine, most clinical studies of this combination have proved to be no more effective than interferon alpha alone, but they have provided evidence of increased toxicity. The recent identification and purification of other biologically active cytokines, such as tumor necrosis factor and interleukin-2, and of monoclonal antibodies that recognize unique cell surface antigens on renal carcinoma cells, provide exciting possibilities for combination regimens with various interferon species.