Hybrid high-dose bolus/continuous infusion interleukin-2 in patients with metastatic renal cell carcinoma: A phase II trial of the national biotherapy study group

Background: Interleukin-2 (IL-2) is an active agent for the treatment of renal cell carcinoma. In animal studies polyethylene glycol conjugated (PEG) IL-2 was found to be effective in certain IL-2-resistant models. When bolus/infusion IL-2 was administered to approximate the pharmacokinetics of PEG-IL-2, resistance was also overcome in these models. Based on these observations, the National Biotherapy Study Group (NBSG) previously had conducted a pilot study (NBSG 90-01) and then a phase I trial off a hybrid regimen of bolus IL-2 followed by continuous IL-2 (NBSG 91-04). Methods: In the current study, NBSG 92-09, a phase II trial was conducted in patients with metastatic renal cell carcinoma using IL-2 at a dose of 36 MIU/m(2) followed by a 72-hour continuous infusion of IL-2 at 18 MIU/m(2) per day, so that over 3 days a total of 90 MIU/m(2) of IL-2 were delivered; the same amount as previously given during 5 days of continuous intravenous (IV) IL-2 at 18 MIU/m(2) per day. This was repeated every 2 weeks for 2 months, and then monthly for up to 4 months. Results: Thirty-one patients with a median age of 62 years were enrolled in this trial. During the first 4 biweekly treatments, the percentages of planned IL-2 administered were 98% for 31 patients, 99% for 27, 98% for 23, and 99% for 20 patients. Toxicities were qualitatively the same as those seem with other IL-2 regimens. During the first 2 months, 4 patients ceased treatment because of rapidly progressive disease while 7 patients stopped because of toxicity; 5 of the 7 were >65 years of age. At the time of formal reassessment after 2 months of treatment, 7 additional patients had progressive disease for a treatment failure rate of 55% prior to monthly maintenance therapy. There were two partial responses among 22 patients who had measurable disease for a response rate of 9%(1 to 29%, 95% CI). Median survival was 10.2 months and failure-free survival (FFS) 3.4 months for the entire group. Conclusion: The response rate seen with this regimen is similar to those of other schedules of IL-2 requiring more prolonged hospitalization. This hybrid bolus/continuous infusion IL-2 schedule appears to be an equally effective and less expensive schedule of IL-2 administration than previously reported inpatient regimens. However it is not likely that this regimen is superior to outpatient combination biotherapy regimens which are currently under investigation.