Adjuvant Subcutaneous Interleukin-2 in Patients with Resected Renal Cell Carcinoma: A Pilot Study

Abstract

Background A pilot study was conducted to investigate the toxicity and tolerance to low-dose subcutaneous interleukin-2 (IL-2) for patients with resected renal cell carcinoma (RCC) at high risk for recurrent disease (TNM stages III and IV resected distant metastases). Patients and Methods Patients with surgically resected locally advanced (T3-4 or N1-2) or metastatic RCC were randomly assigned to 1 of 4 treatment groups that received different dose levels and schedules of subcutaneous IL-2 as follows: dose level 1, 4 MIU/m 2 per day, every other week for 24 weeks (n = 10); dose level 2, 8 MIU/m 2 per day, every other week for 24 weeks (n = 9); dose level 3, 4 MIU/m 2 per day, weeks 1-4, 9-12, and 17-20 (n = 11); and dose level 4, 8 MIU/m 2 per day, weeks 1-4, 9-12, and 17-20 (n = 10). Interleukin-2 was administered in 2 daily doses on days 1-5 of each week indicated. A dose level was considered tolerable if no more than 2 patients experienced grade 3/4 toxicity. Results Forty-one patients were entered in the study and 40 were evaluable for toxicity. Therapy was well tolerated at all dose levels and schedules, with most patients (98%) experiencing mild-to-moderate constitutional symptoms. Grade 3/4 toxicity was seen in 8 patients (20%). Interleukin-2 dose reductions were required in 7 patients, and no patient discontinued therapy secondary to toxicity. Of 39 patients evaluable for efficacy, 31 have experienced relapse (79%), and 15 have died (38%). Median survival was 1.4 years, and the 3-year disease-free survival rate was 33%. Median overall survival has not been reached; however, the 3-year survival rate was 70%. There was no statistically significant difference between any of the treatment arms with respect to disease-free survival or 3-year survival ( P > 0.54 and P ≥ 0.09 for all pairwise comparisons), schedules (dose level 1/2 vs. 3/4; P = 0.46 and P = 0.5), or dose of IL-2 administered (dose level 1/3 vs. 2/4; P = 0.99 and P = 0.1). Conclusion Subcutaneous IL-2 was well tolerated for 6 months in patients with surgically resected RCC at high risk of recurrence. Future adjuvant trials in this setting are not likely to include IL-2 in view of the clinical efficacy and favorable toxicity profiles of selected multitargeted kinase inhibitors.