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
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
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.