Three-weekly docetaxel (T) plus capecitabine (X) in 1st and 2nd line metastatic esophageal cancer (MEC): Final Results of the phase II DACAPO Trial

Abstract

4142 Background: Both X and T have single agent activity in upper gastrointestinal tumors, and have together demonstrated preclinical synergy and a survival benefit in breast cancer. Phase II trials of XT have shown response rates of 40–53% and good tolerability in 1st-line metastatic gastric cancer (ASCO 04, abstracts 4051 and 4057). This trial assessed the efficacy and feasibility of XT combination in patients (pts) with MEC. Methods: Pts received T 75mg/m2 day 1 plus oral X 1000mg/m2 twice a day d1–14 every 3 weeks. The primary endpoint was response according to RECIST. Toxicity was reported according to NCI.CTCAE v3.0. Median follow up is 16.5 (7.9–21.4) months. Results: From 02/03 until 04/04 we included 24 pts in one center: 21 men, 3 women; median age 61.5 years, range 49–72; 17 had squamous cell and 7 adenocarcinomas. All pts had metastatic disease. 16 pts were treated in 1st-line, 8 in 2nd-line. Pts received a median of 4 (0–6) cycles. Dose reductions of one or both agents (to <80% of initial doses) were reported in 41% of pts. 2/24 (8.3%) pts died within 60 days after inclusion: one rapid tumor progression with upper gastrointestinal bleeding, one esophageal stent dislocation with subsequent mediastinitis. Severe adverse events (grade 3/4) reported were: neutropenia 10 (42%), febrile neutropenia 2 (8%), diarrhea 3 (13%), sensory neuropathy 3 (13%), fatigue 2 (8%), hand-foot syndrome 7 (29%). Grade1/2 sensory neuropathy was reported in 7 pts (29%) and hand-foot syndrome in 7 pts (29%). Intent-to-treat efficacy analysis showed a 46% response rate including 1 CR, 17% SD, 29% PD and 8% NE. Of the 11 responses, 9/16 (56%) were in 1st-line pts and 2/8 (25%) in 2nd-line therapy. Median survival is 16.0 months (95%CI 7.9–24.2). Median time to progression is 6.2 months (95%CI 4.6–7.8). Conclusions: Docetaxel plus capecitabine has a manageable toxicity profile and very promising activity in MEC, at least comparable to other doublet regimens. The combination merits further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis, Roche