Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report.
OBJECTIVE
A randomized prospective study was performed to compare the efficacy and toxicity of high-dose intravenous bolus interleukin-2 (IL-2) and a lower-dose intravenous bolus regimen for the treatment of metastatic renal cell carcinoma (RCC).


METHODS
Between March 1991 and April 1993, 125 patients with metastatic RCC were randomized to receive IL-2 by intravenous bolus every 8 hours at either 720,000 IU/kg (high-dose) or 72,000 IU/kg (low-dose) to the maximum-tolerated number of doses (or a maximum of 15 doses). After approximately 7 to 10 days, both treatment groups were re-treated with a second identical cycle of therapy. Those patients who were stable or responding to treatment 5 to 6 weeks later went on to receive re-treatment with another course (two cycles) of therapy. Response rates and toxicity were determined for the two treatment arms.


RESULTS
One hundred twenty-five patients received a total of 208 courses of therapy. Sixty patients were randomized to receive low-dose, and 65 to receive high-dose IL-2. There were no treatment-related deaths in either arm. There was a greater incidence of grade III or IV thrombocytopenia, malaise, and hypotension in patients who received high-dose IL-2, while patients who received low-dose IL-2 had significantly more infections. Three percent of treatment courses with low-dose IL-2 required vasopressor support, compared with 52% of courses with high-dose IL-2. Patients who received low-dose IL-2 had a 7% complete response (CR) and an 8% partial response (PR) rate, and patients who received high-dose IL-2 had a 3% CR and a 17% PR rate.


CONCLUSIONS
Low-dose intravenous bolus IL-2 represents an effective regimen for the treatment of metastatic RCC, with preliminary results comparable to those observed with high-dose IL-2. Low-dose IL-2 can be administered with significantly fewer complications, reduced use of vasopressor support, and fewer admissions to an intensive care unit (ICU).
Yang
J C
JC
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Topalian
S L
SL
Parkinson
D
D
Schwartzentruber
D J
DJ
Weber
J S
JS
Ettinghausen
S E
SE
White
D E
DE
Steinberg
S M
SM
Cole
D J
DJ
Kim
H I
HI
D000328:Adult; D002292:Carcinoma, Renal Cell / Q000556:secondary / Q000628:therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D007376:Interleukin-2