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 a pproved by the Food and Drug Administration for the treatment of advanced r enal cell carcinoma. This phase II study was designed to evaluate the clini cal 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 mIU 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 achi eving stable disease or a response were treated every 10 weeks for a maximu m of five cycles/ year. Results: Out of 20 study participants 8 patients (4 0%; 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 burde ns. All 3 CR continue to respond after 28+ to 30+ months. With a median fol low-up time of 26 months, the median overall survival duration for all pati ents is 18.0 months (95% confidence interval 12-24 months). Response was ob served to correlate significantly with the IL-2 dose intensity. A dose inte nsity below 1440 mIU m(-2) year(-1) and at least 1440 mIU m(-2) year(-1) co rrelated highly with failure to achieve CR and the successful achieving of CR respectively (P < 0.01). An analysis of the present study database in th e context of five previous similar trials demonstrated a significant correl ation between IL-2 dose intensity and response rate by regression analysis (r(2) = 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-inten sive approach led to a high proportion of durable responses. Further evalua tion of this regimen is warranted.