Kh. Chi et al., Phase II trial of systemic recombinant interleukin-2 in the treatment of refractory nasopharyngeal carcinoma, ONCOL-BASEL, 60(2), 2001, pp. 110-115
Background: Interleukin-2 (IL-2) is a cytokine produced by activated T cell
s, which has shown powerful immunostimulatory and antineoplastic properties
. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated cancer
with abundant lymphocyte infiltration histologically. The activity of IL-2
in the treatment of NPC patients is currently unknown. A phase II study wa
s, therefore, initiated to evaluate the efficacy, toxicity and immunologica
l consequences of intravenous bolus IL-2 in patients with recurrent/metasta
tic NPC. Methods: Between November 1996 and April 1997, 14 patients with re
current/metastatic NPC were entered into the study. Recombinant IL-2 (Prole
ukin, Chiron) was injected by intravenous bolus every 8 h at 72,000 IU/kg f
or a maximum of 15 doses. After 7 days, patients were retreated with a seco
nd identical cycle of therapy. Those patients who were stable or responding
to treatment 5-6 weeks later went on to receive another course (two cycles
) of therapy. All patients received prophylactic antibiotics and antipyreti
c medicine. Response and toxicities were evaluated. Serial plasma level of
TNF-alpha, IL-6, soluble IL-2 receptor, IL-10 and soluble CD8 were determin
ed. Results: Fourteen patients received a total of 34 cycles of therapy. No
response was observed. Fifty percent had stable disease, 50% had progressi
ve disease after a median of two cycles of therapy. There was one treatment
-related death from acute myocardial infarction. Body weight increase (>5%)
occurred in 80% of cycles, and hypotension (BP <80 mm Hg systolic) occurre
d in 53%. Serum creatinine increase (>2 mg%) occurred in 24% of cycles, and
SGOT/SGPT increase (>3 x) in 10% of cycles. Symptoms of somnolence, genera
l malaise, nausea and vomiting, pruritus, xerostomia, desquamation were gen
erally mild to moderate but rapidly reversible. Conclusion: The single moda
lity of intravenous bolus IL-2 at the dose level of 72,000 IU/kg is clinica
lly ineffective in NPC patients. Potential mechanisms of the ineffectivenes
s of IL-2 therapy on NPC patients a re discussed. Copyright (C) 2001 S. Kar
ger AG, Basel.