Journal of Clinical Oncology, Vol 14, 2234-2241, Copyright © 1996 by American Society of Clinical Oncology
Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer
BL Gause, M Sznol, WC Kopp, JE Janik, JW Smith 2nd, RG Steis, WJ Urba, W Sharfman, RG Fenton, SP Creekmore, J Holmlund, KC Conlon, LA VanderMolen and DL Longo
Division of Cancer Treatment, National Cancer Institute, Bethesda, MD, USA. bgause@mail.ncifcrf.gov
PURPOSE: Although high-dose interleukin-2 (IL-2) can produce durable
remissions in a subset of responding patients with renal cell carcinoma
(RCC), this occurs in the setting of significant toxicity. The purpose of
this study is to define the maximum-tolerated dosage (MTD) of IL-2 and
interferon alfa-2a (IFN alpha-2a) that can be administered chronically on
an outpatient basis. PATIENTS AND METHODS: Fifty-three patients with
advanced cancer of variable histology with good prognostic features were
treated in six cohorts. Patients in cohorts one through five received IL-2
(1.5 or 3.0 x 10(6) million units (mU)/m2) Monday through Friday and IFN
alpha-2a (1.5 or 3 x 10(6) mU/m2) daily for a 4-week cycle. In cohort six,
IFN alpha-2a was given three times a week. Immunologic monitoring,
including serum levels of soluble IL-2 receptor (sIL-2R) and neopterin,
flow cytometry, and natural killer cell (NK) activity, were measured.
Patients were evaluated for toxicity, response, and survival. RESULTS:
Almost all patients developed grade I/II toxicities commonly associated
with cytokine therapy. Symptoms were most severe with the first treatment
of each week. Dose-limiting toxicities included grade III fatigue,
hypotension, and creatinine elevations. The MTD was 1.5 mU/m2 daily x 5
given subcutaneously repeated weekly for IL-2 and 1.5 mU/m2 daily
subcutaneously (dose level 3) for IFN. Six of 25 assessable patients with
RCC (24%) achieved a partial response (PR), including four of eight
patients who were previously untreated. There were no objective responses
in patients with other tumors, including 12 melanoma patients. CONCLUSION:
IL-2 and IFN alpha-2a can be given with tolerable toxicities on an
outpatient basis and shows significant activity in patients with metastatic
RCC.
