Randomized Italian multicentric trial comparing cisplatinum and gemcitabine with or without low dose interleukin-2 (IL-2) in advanced non-small cell lung cancer (NSCLC)

Abstract

7139 Background: The prognosis of patients with advanced NSCLC is still unsatisfactory. Like other solid tumors, NSCLC is associated with IL-2-dependent cell-mediated immunodeficiency. Furthermore, lymphocyte count would seem to be an independent prognostic factor because it correlates with overall survival (OS). As IL-2 is a lymphocyte activation- and growth-factor, we hypothesized that protracted subcutaneous administration of low-dose recombinant human IL-2, in addition to a standard chemotherapy regimen, could significantly increase OS in advanced NSCLC patients. Methods: A phase III prospective Italian multicentric trial was conducted to compare cisplatin 100 or 75 mg/m2 (at the discretion of each center) on day 2 + gemcitabine 1000 mg/m2 on days 1 and 8 (CT arm) every 21 days for a maximum of 6 cycles with the same schedule + low-dose subcutaneous IL-2 3,000,000 IU/die on days 3–5, 9–11 and 15–17 (immunoCT arm) as first-line chemotherapy. An a priori sample size of 236 evaluable patients (146 events) was calculated and an interim analysis after the 150th randomized patient to verify the feasibility and the hypothesized event rate in the control group was planned. Patients with histologically/cytologically confirmed stage IIIb or IV non operable NSCLC and measurable disease, ECOG PS 0–2, age 18–70 years and adequate bone marrow, renal and liver function were eligible for the study. Randomization was stratified by center, ECOG PS, stage of disease and percentage of weight loss. Results: Between June 2000 and November 2004, 241 patients were randomized from 21 Italian centers, 114 onto the CT arm and 127 onto the immunoCT arm. Patient characteristics were well balanced between the two arms. Median age was 62 years (range 32–70 years). One third of patients had stage IIIb disease, 44% had PS =0, 50% had PS=1, and only 6% had PS=2. More then 86% of patients had no or <5% weight loss. Conclusions: The interim analysis was carried out only recently due to the accelerated enrolment rate during the final months of recruitment. Data on treatment safety and efficacy for the first 150 recruited patients will be available in a few months’ time. Supported by Chiron Italia. No significant financial relationships to disclose.