Journal of Clinical Oncology, Vol 10, 275-281, Copyright © 1992 by American Society of Clinical Oncology
A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma
GR Weiss, KA Margolin, FR Aronson, M Sznol, MB Atkins, JP Dutcher, ER Gaynor, DH Boldt, JH Doroshow and MH Bar
Extramural IL-2/LAK Working Group, University of Texas Health Science Center/Audie L. Murphy Memorial Veterans Administration Hospital, San Antonio 8284.
PURPOSE: Since 1985, multiple centers have demonstrated that interleukin-2
(IL-2) and lymphokine-activated killer (LAK) cells produce durable
anticancer responses in patients with metastatic renal cell carcinoma.
High-dose recombinant IL-2 (rIL-2) has been administered by intravenous
bolus injection (Rosenberg SA, et al: N Engl J Med 313:1485-1492, 1985) and
by continuous intravenous infusion (West WH, et al: N Engl J Med
316:898-905, 1987) combined with lymphokine-activated killer (LAK) cells,
with both methods producing responses in patients with advanced renal cell
carcinoma. The Extramural IL-2/LAK Working Group has conducted a randomized
phase II trial of two intravenous high-dose rIL-2 regimens (bolus three
times daily or 24-hour continuous infusion) to determine if either one
manifests greater anticancer activity or a more acceptable toxicity
profile. PATIENTS AND METHODS: Ninety-four patients with measurable
advanced renal cell carcinoma were enrolled on this study: 46 to the bolus
injection arm and 48 to the continuous infusion arm. On both arms, patients
underwent a priming phase of rIL-2 administration, four daily
lymphocytaphereses to harvest mononuclear cells that were placed in 3- to
4-day culture for generation of LAK cells, and an rIL-2/LAK
coadministration phase. Patients were then observed monthly for evidence of
response to this therapy and were offered up to two additional courses of
treatment every 3 months if evidence of response was detected. RESULTS:
Twenty percent of patients on the bolus injection arm experienced objective
responses (three complete responses and six partial responses); 15% of
patients on the continuous infusion arm responded (two complete responses
and five partial responses). Complete responses were durable, persisting
for 310+ to 700+ days. The incidence of severe life-threatening toxicities
typical of high-dose rIL-2 therapy was similar in both arms (eg, patients
with hypotension requiring pressors: bolus 71%, continuous 63%; oliguria
less than or equal to 200 mL/8 hours: bolus 65%, continuous 71%). More
episodes of fever, infection, and serum alkaline phosphatase elevation were
associated with the continuous infusion arm, while more thrombocytopenia
occurred on the bolus injection arm. Four patients (three bolus injection,
one continuous infusion) died of respiratory and circulatory failure while
under treatment. No clinical or laboratory parameter accompanying treatment
on either arm was, by univariate or multivariate analysis, associated with
an increased likelihood of response. CONCLUSIONS: Both methods of high-dose
rIL- 2/LAK cell administration produce nearly equivalent anticancer
activity and toxicity in the treatment of renal cell carcinoma. The ability
to predict responding patients based on patient or treatment
characteristics is not possible.
