OBJECTIVES: This study evaluates the efficacy and toxicity of single-agent irinotecan following hepatectomy for metachronous colorectal metastases, and examines the predictive value of p27 and p53 expression and of microsatellite instability (MSI) status. METHODS: Twenty-nine patients, previously treated with 5-fluorouracil, with operable hepatic colorectal metastases underwent hepatectomy and received adjuvant irinotecan (thrice weekly) for 6 planned cycles. Metastases were examined for p53 and p27 expression by immunohistochemistry and for MSI using mono- and dinucleotide markers. RESULTS: The starting dose of irinotecan was 350 mg/m2 (in 3 patients), 300 mg/m2 (n = 14), and 250 mg/m2 (n = 12). Four patients failed to complete 6 cycles (2 progressive disease and 2 toxicity). Grade > or =3 toxicity was experienced in 8% of cycles (13 of 165). The estimated median relapse-free survival (RFS) was 45.2 months. RFS at 18 months was estimated to be 59% (95% confidence interval [CI], 43-80), 2-year overall survival (OS) was 85% (95% CI, 72-99.8), and the median follow-up was 27.9 months. Six patients (21%) have died; median OS has not been reached. In univariate analyses, p27 and MSI status were not predictive for RFS while p53 approached statistical significance (P = 0.051). Duration of chemotherapy was the only significant predictive factor (P = 0.006). CONCLUSION: The tolerability of this regimen after major liver resection supports further evaluation of irinotecan-based adjuvant chemotherapy in this group of patients.
OBJECTIVES: This study evaluates the efficacy and toxicity of single-agent irinotecan following hepatectomy for metachronous colorectal metastases, and examines the predictive value of p27 and p53 expression and of microsatellite instability (MSI) status. METHODS: Twenty-nine patients, previously treated with 5-fluorouracil, with operable hepatic colorectal metastases underwent hepatectomy and received adjuvant irinotecan (thrice weekly) for 6 planned cycles. Metastases were examined for p53 and p27 expression by immunohistochemistry and for MSI using mono- and dinucleotide markers. RESULTS: The starting dose of irinotecan was 350 mg/m2 (in 3 patients), 300 mg/m2 (n = 14), and 250 mg/m2 (n = 12). Four patients failed to complete 6 cycles (2 progressive disease and 2 toxicity). Grade > or =3 toxicity was experienced in 8% of cycles (13 of 165). The estimated median relapse-free survival (RFS) was 45.2 months. RFS at 18 months was estimated to be 59% (95% confidence interval [CI], 43-80), 2-year overall survival (OS) was 85% (95% CI, 72-99.8), and the median follow-up was 27.9 months. Six patients (21%) have died; median OS has not been reached. In univariate analyses, p27 and MSI status were not predictive for RFS while p53 approached statistical significance (P = 0.051). Duration of chemotherapy was the only significant predictive factor (P = 0.006). CONCLUSION: The tolerability of this regimen after major liver resection supports further evaluation of irinotecan-based adjuvant chemotherapy in this group of patients.
Authors: Marc Ychou; David Azria; Cathy Menkarios; Patrick Faurous; François Quenet; Bernard Saint-Aubert; Philippe Rouanet; Monique Pèlegrin; Caroline Bascoul-Mollevi; Dominique Guerreau; Jean-Claude Saccavini; Jean-Pierre Mach; Jean-Claude Artus; André Pèlegrin Journal: Clin Cancer Res Date: 2008-06-01 Impact factor: 12.531