Interferon alfa and IL-2

Cytokine therapy with interferon alfa or IL-2 has been shown to induce objective responses. Interferon alfa appears to have a modest impact on survival in selected patients. Interferon alfa has approximately a 15% objective response rate in appropriately selected individuals.[16] In general, these patients have nonbulky pulmonary or soft tissue metastases with excellent performance status ratings of 0 or 1, according to the Eastern Cooperative Oncology Group (ECOG) rating scale, and the patients show no weight loss. The interferon alfa doses used in studies reporting good response rates have been in an intermediate range (6–20 million units administered 3 times weekly). A Cochrane analysis of six randomized trials, with a total of 963 patients, indicated an HR for survival of 0.78 (0.67–0.90) or a weighted average improvement in survival of 2.6 months.[16][Level of evidence A1]

High-dose IL-2 produces an overall response rate similar to that of interferon alfa, but approximately 5% of the patients have shown durable complete remissions.[20,39-43] No randomized controlled trial of IL-2 has shown a longer survival result. High-dose IL-2 is used because it is the only systemic therapy that has been associated with inducing durable complete remissions, albeit in a small fraction (about 5%) of patients who are eligible for this treatment. The optimum dose of IL-2 is unknown. High-dose therapy appears to be associated with higher response rates but with more toxic effects. Low-dose inpatient regimens show activity against renal cell carcinoma with fewer toxic effects, especially hypotension, but have not been shown to be superior to placebo or any alternative regimen in terms of survival or quality of life (QOL).[21] Outpatient subcutaneous administration has also demonstrated responses with acceptable toxic effects but, again, with unclear survival or QOL benefit.[44] Combinations of IL-2 and interferon alfa have been studied, but outcomes have not been better than with high-dose or low-dose IL-2 alone.[17,45]