Systemic therapy for renal cell carcinoma

Purpose: We review the status of systemic therapy for patients with advance d renal cell carcinoma. Materials and Methods: A literature search was performed on MEDLINE and CAN CERLIT to identify results of systemic therapy for patients with renal cell carcinoma published from January 1990 through December 1998. Treatment res ults of chemotherapy agents, immunotherapy, combination programs and adjuva nt therapy were reviewed. Results: No chemotherapy agent has produced response rates that justify its use as a single agent. Interferon-alpha and interleukin (IL)-2 demonstrate d low response rates ranging from 10% to 20%. The results of 2 randomized t rials suggest that treatment with interferon-alpha compared to vinblastine or medroxyprogesterone achieves a small improvement in survival. Response r ates in patients treated with low dose IL-2 are similar to those achieved w ith a high dose bolus schedule but whether the responses are as durable is being addressed in an ongoing randomized trial. A randomized trial of inter feron-alpha plus IL-2 compared to monotherapy with either agent showed incr eased toxicity but no improvement in survival. In 3 randomized trials no su rvival benefit was associated with adjuvant interferon-a therapy following complete resection of locally advanced renal cell carcinoma. Conclusions: Despite extensive evaluation of many different treatment modal ities, metastatic renal cell carcinoma remains highly resistant to systemic therapy. A few patients exhibit complete or partial responses to interfero n and/or IL-2 but most do not respond, and there are few long-term survivor s. Preclinical research, and clinical evaluation of new agents and treatmen t programs to identify improved antitumor activity against metastases remai n the highest priorities in this refractory disease.