A multi-center phase II study and biomarker analysis of combined cetuximab and modified FOLFIRI as second-line treatment in patients with metastatic gastric cancer

摘要

s Background To evaluate the efficacy of cetuximab combined with modified FOLFIRI (mFOLFIRI) as a second-line treatment in metastatic gastric cancer patients and to identify potential biomarkers of clinical outcomes. Methods All 61 patients received an initial intravenous (IV) dose of cetuximab (400?mg/m2) and weekly doses (250?mg/m2) thereafter, starting on day 1. On day 2 of each 14-day period, patients received IV irinotecan (180?mg/m2), leucovorin (200?mg/m2), and an IV bolus dose of 5-FU (400?mg/m2) followed by a continuous infusion of 5-FU (2400?mg/m2) for 46?h. The primary endpoint was time-to-progression (TTP). Results The response rate (RR) was 33.3% among 54 evaluable patients. In the intention-to-treat analysis, median TTP was 4.6?months (95% confidential interval [CI]: 3.6-5.6?months) and median overall survival (OS) was 8.6?months (95% CI: 7.3-9.9?months). In univariate analyses, plasma vascular endothelial growth factor (VEGF) levels were correlated with clinical outcome. In patients with low (≤12.6?pg/ml) and high (>12.6?pg/ml) baseline plasma VEGF levels, RR values were 55.0% and 5.3%, respectively ( P =?0.001); median TTP values were 6.9?months and 2.8?months, respectively (P?=?0.0005); and median OS values were 12?months and 5?months, respectively ( P Conclusions Combination therapy comprising cetuximab and mFOLFIRI was well tolerated and active as a second-line treatment for patients with metastatic gastric cancer. Patients with low baseline plasma VEGF levels were associated with better clinical outcomes. Trial registration ClinicalTrials.gov. NCT00699881 . Registered 17 June 2008 (retrospectively registered)