Clinical and Immunomodulatory Effects of Combination Immunotherapy with Low- Dose Interleukin 2 and Tumor Necrosis Factor a. in Patients with Advanced Non-Small Cell Lung Cancer: A Phase I Trial

Sixteen patients with metastatic non-small cell lung cancer were treated with a combination of simultaneous low-dose interleukin 2 (IL-2) and tumor necrosis factor a. The purpose of this phase I dose escalation trial was to assess the clinical toxicities, immunomodulatory effects, and antitumor efficacy of this combination. Patients received a continuous daily i.v. infusion of 6 x 11)'1U /nr of IL-2 for 5 days and a concomitant daily ¡.in.dose of tumor necrosis factor a on each day of IL-2 adminis tration. Tumor necrosis factor a administration started at a dose of 25 Mg/m2/day (level I) for seven patients, 50 wg/iir <la>(level II) for seven patients, and 100 ¿ig/m2/day(level III) for two patients. Treatment was given at 3-week intervals. Only one patient required monitoring by an intensive care unit during therapy. Major toxic effects included fever, local skin reaction at the i.m. injection site, pancytopenia, and general malaise, all of which were reversible within 48 h of cessation of therapy. Dose level II was determined to be the maximum tolerated dose, with the dose-limiting toxicity being thrombocytopenia (<50, 000/*il). In 12 Ã