Medical treatment of advanced renal cell carcinoma: present options and future directions

The treatment of patients with metastatic renal cell carcinoma (MRCC) continues to be disappointing. A large number of hormones, chemotherapeutic agents and combinations have been tested with poor and non-reproducible results. Among the immunological treatments investigated in MRCC, the best results have been claimed with interferons (IFNs) and interleukin-2 (IL-2) and, although no randomized studies have shown higher activity than cytotoxic drugs, hormones or even no treatment, many oncologists feel it justified to consider these biologic agents the treatment of choice for this disease. Of patients treated with alpha-IFN, 15-20% achieve an objective remission and 3-5% achieve a long-lasting complete response. No substantial increase of the therapeutic activity of alpha-IFN was produced by combination with chemotherapeutic agents and gamma-IFN or tumour necrosis factor. High doses of IL-2 with or without lymphokine-activated killer cells led to successful results in about 20-30% of patients with 5-10% complete responses. More recently, less toxic regimens with lower doses of IL-2 alone or combined with alpha-IFN produce similar response rates. Many studies have clarified the importance of prognostic factors in patient selection for response and survival during treatments with IFNs and IL-2. Good performance status, a long interval from diagnosis to treatment, and only one site of disease seem to be the most important predictors for survival. Both IFNs and IL-2 appear to possess encouraging antitumour activity in patients with favourable prognostic factors, but further studies are needed to identify the treatment of choice, the optimal dose regimen and route of administration in this subgroup of patients. Patients with poor prognosis should be encouraged to enter controlled studies aimed to evaluate investigational drugs and new therapeutic methods.