Randomized, phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated, extensive-stage (ES) small cell lung cancer (SCLC)

Abstract

LBA7004 Background: EP has been standard treatment for ES SCLC. A phase III study reported improved overall survival (OS) for pts receiving IP vs. EP (Noda et al NEJM ‘02). The current trial was designed to confirm these results using a modified weekly regimen of IP vs EP, enabling improved tolerability and greater dose intensity. Methods: The 1° endpoint of this multicenter, open-label, randomized, prospective trial in chemonaive pts with ES SCLC was to compare OS of IP vs EP. Eligible pts had ECOG PS 0–1 and adequate organ function. Pts with uncontrolled brain mets were excluded. Pts were randomized 2:1 [stratified by gender, LDH (≤ ULN or > ULN), and age (<65 or ≥ 65)] to: IV cisplatin 30 mg/m2 + irinotecan 65 mg/m2, days 1,8 every 21 days (arm A); or IV cisplatin 60 mg/m2, day 1, and IV etoposide 120 mg/m2, days 1–3 every 21 days (arm B) for 4 cycles, or PD, or intolerable toxicity. A sample size of 300 (200 arm A;100 arm B) was planned to achieve 80% power to detect a 30% OS improvement (from 37%–50% at 1 yr). Primary analysis is planned after Dec 31, 2004, 18 months after the last pt enrollment. Results: Of 336 pts randomized between 12/00–6/03, 330 were treated (221/109 in arms A/B). Baseline demographics were similar in both arms: 57% male;median age 63;PS 1∼66%. In both arms, 65% of pts received ≥4 cycles. There are 278 deaths to date. Selected grade 3/4 toxicities in arms A/B were: diarrhea (21 vs 0%), neutropenia (35 vs 84%), febrile neutropenia (4 vs11%), anemia (5 vs11%), thrombocytopenia (4 vs19%). OS and response data will be presented using Kaplan-Meier methodology and Cox models. Conclusions: IP had significantly less myelosuppression, but more diarrhea than EP. The primary endpoint will be analyzed before March 25, 2005 and will be presented at the ASCO meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer, Pharmacia Pfizer Pfizer, Pharmacia