The Journal of Thoracic and Cardiovascular Surgery, Vol 99, 8-12, Copyright © 1990 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
Combination immunotherapy for non-small cell lung cancer. Results with interleukin-2 and tumor necrosis factor-alpha
SC Yang, L Owen-Schaub, A Mendiguren-Rodriguez, EA Grimm, WK Hong and JA Roth
Department of Thoracic Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Sixteen patients with advanced non-small cell lung cancer were treated with
a combination of low-dose interleukin-2 and tumor necrosis factor- alpha.
Patients received a continuous 24-hour intravenous infusion of
interleukin-2 at 1 X 10(6) Cetus U/m2 and a simultaneous daily
intramuscular dose of tumor necrosis factor-alpha (25 to 100 micrograms/m2)
for 5 consecutive days. These doses did not have antitumor activity when
administered alone in previous trials. Treatment was given at 3-week
intervals. Common side effects included fever, local skin reaction at the
injection site of tumor necrosis factor-alpha, pancytopenia, and general
malaise, all of which were reversible within 48 hours of cessation of
therapy. The maximum tolerated doses with this combination were 1 X 10(6)
U/m2/day of interleukin-2 and 50 micrograms/m2/day of tumor necrosis
factor-alpha, with thrombocytopenia (less than 50K) being the dose-limiting
toxicity. Twelve patients received two cycles or more and were evaluable
for response. Measurable tumor regression occurred in four patients. An
additional seven patients had radiographic stabilization of disease (median
= 12 weeks) before progression. All patients had augmented
lymphokine-activated killer and natural killer activity during therapy.
Enhanced lysis of autologous tumor in vitro was demonstrated in four of
four patients during therapy. We conclude that combination immunotherapy
with low-dose interleukin-2 and tumor necrosis factor- alpha can mediate
tumor regression and can be given with acceptable toxicity.
