SAN FRANCISCOTrials employing outpatient use of subcutaneous (SC) interleukin-2 (IL-2, Proleukin) in lower doses suggest that the overall response rate in metastatic renal cell carcinoma is adversely affected by the decrease in dose or the subcutaneous route of administration.
In a preliminary analysis of phase III data comparing the best high-dose treatment (IL-2 alone) with the best outpatient regimen (IL-2/interferon-alfa [IFN-alfa-2b, Intron A]) for metastatic disease, researchers from the Cytokine Working Group reported a trend toward improved responses in patients assigned to the high-dose regimen.
David McDermott, MD, of Deaconess Medical Center, Boston, presented the study at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 685).
Interleukin-2 is a cytokine that is thought to exert its major antitumor effect through lymphocyte activation. High-dose IL-2 was FDA-approved in 1992; currently, it is the only approved treatment for patients with metastatic kidney cancer.
Previous studies of IL-2 indicated durable high-quality responses in approximately 10% of patients with renal cell carcinoma. Use of the cytokine, however, sometimes produces life-threatening toxicities. Large bolus doses of IL-2 are associated with the capillary leak syndrome and require vigilant inpatient monitoring. High-dose IL-2 should be administered at a facility where the staff is experienced in dealing with the toxicities of this agent.
Various studies have attempted different doses and alternate routes to mitigate its significant toxicities. Tests of subcutaneous IL-2 therapy in the clinic looked promising.
Dr. McDermott cited sequential phase II studies published in the Cancer Journal of Scientific American in 1997 that found a similar response rate (ranging from 11% to 17%) and median survival (15 to 20 months) for low-dose outpatient IL-2/IFN. This is significant because of the expense and inconvenience of intravenous dosing compared with subcutaneous doses self-administered at home.