Hybrid high-dose bolus continuous infusion interleukin-2 in patients with metastatic melanoma: A phase II trial of the Cancer Biotherapy Research Group (formerly the National Biotherapy Study Group)

Purpose: Interleukin-2 (IL-2) is an active agent for the treatment of melanoma. In animal studies, polyethylene glycol conjugated (PEG) IL-2 was found to be effective in certain IL-2-resistant models. Bolus/infusional IL-2 administered to approximate the pharmacokinetics of PEG-IL-2 also overcame resistance in these models. Based on these observations, the Cancer Biotherapy Research Group (CBRG) [formerly the National Biotherapy Study Group (NBSG)] previously had conducted a pilot study and then ap,tra;se I trial of bolus IL-2 followed by continuous IL-2 (NBSG 90-01). Methods: In the current study, NBSG 92-09, a phase II trial was conducted 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)/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 IV IL-2 at 18 MIU/m(2) day. This schedule was repeated every 2 weeks for 2 months, and then monthly for zip to 6 months. Results: Twenty-two patients with metastatic melanoma were enrolled in this trial Toxicities were qualitatively similar to those seen with other IL-2 regimens, bus grade 3 and 4 toxicities were observed only in patients who received at least four cycles of treatment,. only one patient went off study because of toxicity. For 18 patients with measurable disease, there were two complete and two partial responses in patients ages 32, 66, 72 and 83 years for a response rate of 22% (6% to 18%; 95% confidence interval [Ci]). The median survival for all 21 evaluable patients enrolled in the trial was 8.5 months. Conclusion: The hybrid schedule of drug delivery in NBSG 92-09 allowed the same nose and intensity of IL-2 to be delivered over 3 days instead of 5 days which resulted in fewer days of hospitalization and therefore decreased cost; but with no increase in toxicity and no decrease in efficacy in patients with metastatic melanoma.