A phase II trial of dose-intensive interleukin-2 in metastatic renal cell carcinoma.

Purpose: High-dose bolus interleukin-2 (IL-2) is currently the sole agent approved by the Food and Drug Administration for the treatment of advanced renal cell carcinoma. This phase II study was designed to evaluate the clinical activity and toxicity spectrum of a regime consisting of dose-intensive IL-2 in both previously treated and untreated patients with advanced renal cell carcinoma.

Patients And Methods: Twenty eligible, sequential patients received IL-2 at a dose of 24 mlU m(-2) dose(-1) (1.33 mg m(-2) dose(-1)) every 8 h on days 1-5 and 15 19, for a maximum of 28 boluses. Patients achieving stable disease or a response were treated every 10 weeks for a maximum of five cycles/year.

Results: Out of 20 study participants 8 patients (40%; 95% confidence interval, 18.5%-61.4%) demonstrated a response. Three of these responses were complete (CR; 15%) while 5 were partial (PR; 25%) and about 75% of the responses occurred in patients with extensive tumor burdens. All 3 CR continue to respond after 28+ to 30+ months. With a median follow-up time of 26 months, the median overall survival duration for all patients is 18.0 months (95% confidence interval 12-24 months). Response was observed to correlate significantly with the IL-2 dose intensity. A dose intensity below 1440 mlU m(-2) year(-1) and at least 1440 mlU m(-2) year(-1) correlated highly with failure to achieve CR and the successful achieving of CR respectively (P < 0.01). An analysis of the present study database in the context of five previous similar trials demonstrated a significant correlation between IL-2 dose intensity and response rate by regression analysis (r=0.89; P < 0.019). Finally, all toxicities were reversible once the dosing had concluded.

Conclusions: IL-2 dose intensity appears to represent a significant determinant of successful clinical outcomes. This dose-intensive approach led to a high proportion of durable responses. Further evaluation of this regimen is warranted.