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IL-2 BOLUS DOSING IS MORE EFFECTIVE THAN CONTINUOUS INFUSION

Executive Summary

IL-2 BOLUS DOSING IS MORE EFFECTIVE THAN CONTINUOUS INFUSION, National Cancer Institute Surgery Branch Chief Steven Rosenberg, MD, asserted at the first Interleukin-2 International Symposium, held Nov. 11-12 in Amsterdam, the Netherlands. "There's been confusion about whether or not there's a difference in toxicity between the bolus administration of IL-2 and continuous infusion of IL-2," Rosenberg said. "In fact, there's no difference in toxicity." The NCI scientist referred to other symposium participants whose research focused on continuous infusion administration. "For some reason, essentially every report at this meeting used what I considered to be suboptimal schedules...utilizing the continuous administration of IL-2 at a maximum tolerated dose of 3x107 Cetus units per meter2, which allows administration of a third to a fifth of the amount of IL-2 that we would give by bolus infusion," he said. "We picked bolus administration because that's what works in experimental animals," Rosenberg explained. With continous infusion of IL-2, "there's no experimental animal data that it works, to my knowledge...not a single paper." The researcher noted that animal data also shows that there is "a linear relationship between the amount of IL-2 administered to animals with advanced invasive cancer and the tumor reduction." The data "would lead us to conclude that the more IL-2 you give the better." Out of 400 patients that have been treated with high-dose IL-2, Rosenberg reported that there has been a 1.9% treatment-related mortality. In Rosenberg's IL-2/LAK (lymphokine activated killer cell) trial with 175 patients, there has been a complete response rate of 10% and a partial response rate of 20% in renal cell carcinoma, and a 10% complete response rate in melanoma, he reported. Responding to the charge that many of his patients have needed intensive care therapy due to the severe toxicity of larger doses of IL-2, Rosenberg maintained that "it is an unusual patient that we put into intensive care with our bolus schedule." He stated that in both the continuous infusion regimen and the bolus regimen, "you're pushing patients to maximum toxicity," however, "you're just giving a lot less IL-2 by continuous infusion."

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