Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 4006
© 2004 American Society of Clinical Oncology

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Abstract

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

Memorial Sloan-Kettering Cancer Center, New York, NY; St. Luc Hospital, Montreal, PQ, Canada; Intermountain Hematology & Oncology Associates, Salt Lake City, UT; Arizona Clinical Research Center, Inc., Tuscon, AZ; Duke University Medical Center, Durham, NC; Pacific Shores Medical Group, Long Beach, CA; Daiichi Pharmacetical Corporation, Montvale, NJ; University of Colorado - Health Sciences Center, Denver, CO

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 monitoring board monitored the trial. RESULTS: From 8/01 to 1/03, 349 patients were randomized, 175 to DX + GEM, and 174 to GEM alone. Twenty-four pts (6.9%) were not treated. The treatment arms were well-balanced for extent of disease, KPS, and prior RT. The median survival time was 6.7 months for DX + GEM and 6.2 months for GEM alone (p=0.52). The median TTP for DX + GEM was 3.7 months and 3.8 months for GEM alone (p=0.22). There was an improvement in time-to-worsening of pain and analgesic consumption for DX + GEM compared to GEM alone. However, time-to-worsening of KPS and weight were similar for both treatment arms. Tumor response rates were 8.2% for DX + GEM and 6.3% for GEM alone. Grade 3–4 toxicity was higher for the DX + GEM arm for neutropenia (30% vs 15%, p=0.001), thrombocytopenia (17% vs 4%, p=0.0004) and vomiting (11% vs 5%, p=0.04). The rates of febrile neutropenia were 4% for DX + GEM and 2% for GEM alone, p=0.24. The relative dose-intensities were similar for both arms: 83% and 81% of projected doses for the DX and GEM arm compared to 92% for GEM alone. CONCLUSIONS: DX + GEM was not superior to GEM alone with respect to overall survival in the front-line treatment of APC. There was a trend in favor of clinical benefit for the combination arm. The results do not alter the standard of care for treatment of APC.

Author Disclosure

Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi Pharma, Ltd., Daiichi Pharmaceuticals Daiichi Pharmaceuticals Daiichi Pharma, Ltd.

Abstract presentation from the 2004 ASCO Annual Meeting