Gefitinib (G) plus Interleukin-2 (IL-2) in previously treated patients with advanced non-small-cell lung cancer (NSCLC)

Background: Previous studies in patients with NSCLC treated with IL-2 reported relatively long survival (Cancer 1994;73:1353–60) and a recent study indicated that lymphocytes are activated by G treatment (J Cancer Res Clin Oncol. 2006;132:719- 725.). In this study we explored the possible synergism between IL-2 and G in terms of response rate, survival and toxicity. Methods: From September 2003 to November 2006, 70 consecutive chemotherapy treated patients with advanced, progressive NSCLC received oral G 250 mg daily in a compassionate use program at a single institution. The first 39 patients included in the study received only G, the others 31 also received subcutaneous IL-2: 1 MUI/m2 twice a day on day 1 and 2, once a day on day 3, 4, 5 every week for 4 consecutive weeks with 4 week rest period. This is a phase II trial combined with a cohort design each having a different outcome event. All the evaluations were made using Recist criteria and according to the intention to treat principle. Results: The main patients characteristics and results are showed in the table below. Fifty-one (73%) patients received one prior chemotherapy regimen, while 17 (24%) received = two prior lines of treatment. *Median, months ±95% CI. §p value<0.05 Cox’s regression analysis, including PS, gender, smoke, skin toxicity, histology and use of IL-2, revealed that only skin toxicity [p<0.001; HR 0.29;CI 95% 0.16–0.54] and use of IL-2 [p<0.001; HR 0.33;CI 95% 0.18–0.60] were significantly associated with improvement in OS. Patients treated with IL-2 also showed grade 2–3 fever in 46%, fatigue in 21%, arthralgias in 13%, besides the known G- related toxicity. Conclusions: In this consecutive, non-randomized, series of patients, the use of IL-2 seems to increase the efficacy of G. Further randomized studies of TK inhibitors with IL-2 are warranted.