A randomized phase III trial of DX-8951f (Exatecan Mesylate; DX) and Gemcitabine (GEM) vs. Gemcitabine alone in advanced pancreatic cancer (APC)

Abstract

4006 BACKGROUND: DX is a novel hexacyclic, water-soluble, topoisomerase-1 inhibitor. DX has single-agent and combination activity with GEM in APC (D'Adamo, et al. ASCO, 2001; O'Reilly, et al. ASCO, 2002). A multicenter, randomized phase III trial comparing DX + GEM to GEM alone in APC was conducted. METHODS: Eligibility included KPS ≥ 60%; locally advanced or metastatic pancreatic adenocarcinoma; no prior chemotherapy. Radiation (RT) alone for locally advanced disease was permitted. Patients (pts) were randomized on a 1: 1 basis to DX + GEM or GEM alone. Pts were stratified by KPS, 60%, 70–80%, ≥ 90%, locally advanced vs metastatic disease, prior RT vs. no RT. For the DX + GEM arm, DX was dosed at 2.0mg/m2; GEM at 1,000mg/m2 on a days 1 and 8, q 3 weeks. GEM alone was dosed at 1,000mg/m2 up to 7 weeks in the 1st cycle, then weekly x 3, q 4 weeks. Tumor assessment was performed every 6 weeks. The primary endpoint was overall survival. An intent-to-treat analysis was used. An independent data safety monitor...