A Zaanan1, P Cuilliere-Dartigues2, A Guilloux3, Y Parc4, C Louvet1, A de Gramont1, E Tiret5, S Dumont6, B Gayet7, P Validire8, J-F Fléjou2, A Duval3, F Praz9. 1. INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Medical Oncology. 2. INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Pathology. 3. INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre. 4. INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of General and Digestive Surgery, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris. 5. UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of General and Digestive Surgery, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris. 6. Institut Fédératif de Recherche65, UPMC Univ Paris 06. 7. Department of Digestive Disease Medical Surgery. 8. Department of Pathology, Institut Mutualiste Montsouris, University Paris Descartes, Paris, France. 9. INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre. Electronic address: francoise.praz@upmc.fr.
Abstract
BACKGROUND: The aim was to determine the values of p53 tumour expression and microsatellite instability (MSI) phenotype to predict benefit from adjuvant chemotherapy of colon cancer by 5-fluorouracil and leucovorin (FL) alone or with oxaliplatin (FOLFOX). PATIENTS AND METHODS: This retrospective study included 233 unselected patients with stage III colon cancer treated by FL (n = 124) or FOLFOX (n = 109). The impact of p53 expression and MSI on disease-free survival (DFS) was defined using univariate and multivariate analyses. A Cox proportional hazards model was specifically designed to evaluate the interaction between chemotherapy and these genetic alterations. RESULTS: In univariate analyses, addition of oxaliplatin significantly improved DFS provided that tumour overexpressed p53 [hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.19-0.82; P = 0.01] or displayed MSI phenotype (HR 0.17; 95% CI 0.04-0.68; P = 0.01). In multivariate analyses, p53 was confirmed as an independent factor predictive of benefit from FOLFOX (P = 0.03), while the interaction of MSI with chemotherapy could not be determined in the absence of relapse in the MSI group treated with FOLFOX. CONCLUSION: Our observations indicate that MSI status and p53 expression may influence the impact of oxaliplatin on adjuvant treatment of stage III colon cancer patients.
BACKGROUND: The aim was to determine the values of p53tumour expression and microsatellite instability (MSI) phenotype to predict benefit from adjuvant chemotherapy of colon cancer by 5-fluorouracil and leucovorin (FL) alone or with oxaliplatin (FOLFOX). PATIENTS AND METHODS: This retrospective study included 233 unselected patients with stage III colon cancer treated by FL (n = 124) or FOLFOX (n = 109). The impact of p53 expression and MSI on disease-free survival (DFS) was defined using univariate and multivariate analyses. A Cox proportional hazards model was specifically designed to evaluate the interaction between chemotherapy and these genetic alterations. RESULTS: In univariate analyses, addition of oxaliplatin significantly improved DFS provided that tumour overexpressed p53 [hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.19-0.82; P = 0.01] or displayed MSI phenotype (HR 0.17; 95% CI 0.04-0.68; P = 0.01). In multivariate analyses, p53 was confirmed as an independent factor predictive of benefit from FOLFOX (P = 0.03), while the interaction of MSI with chemotherapy could not be determined in the absence of relapse in the MSI group treated with FOLFOX. CONCLUSION: Our observations indicate that MSI status and p53 expression may influence the impact of oxaliplatin on adjuvant treatment of stage III colon cancerpatients.
Authors: O Vondálová Blanářová; I Jelínková; A Hyršlová Vaculová; P Sova; J Hofmanová; A Kozubík Journal: Cell Prolif Date: 2013-09-30 Impact factor: 6.831