5-Fluorouracil Adjuvant Chemotherapy Does Not Increase Survival in Patients With CpG Island Methylator Phenotype Colorectal Cancer
| Autor: | Xavier Bessa, Artemio Payá, Estefanía Rojas, Lucía Pérez–Carbonell, Juan Clofent, C. Richard Boland, Thuy Nguyen, Antoni Castells, Cristina Alenda, Rodrigo Jover, Rosa M. Xicola, David Nicolás Pérez, Xavier Llor, Joaquín Cubiella, Ajay Goel, Pedro Zapater, Montserrat Andreu, Juan Diego Morillas, Francesc Balaguer, Luis Bujanda, Josep Maria Reñe |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Oncology Antimetabolites Antineoplastic medicine.medical_specialty Colorectal cancer medicine.medical_treatment Population Kaplan-Meier Estimate Disease-Free Survival Article Cohort Studies Predictive Value of Tests Internal medicine medicine Humans education neoplasms Aged Proportional Hazards Models Aged 80 and over education.field_of_study Chemotherapy Hepatology CpG Island Methylator Phenotype Proportional hazards model business.industry Hazard ratio Gastroenterology Microsatellite instability DNA Methylation Middle Aged Prognosis medicine.disease digestive system diseases Surgery Phenotype Chemotherapy Adjuvant Fluorouracil CpG Islands Female Colorectal Neoplasms business Follow-Up Studies medicine.drug |
| Zdroj: | Gastroenterology. 140:1174-1181 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2010.12.035 |
| Popis: | Background & Aims 5-Fluorouracil (5-FU)–based adjuvant chemotherapy does not increase survival times of patients with colorectal tumors with microsatellite instability. We determined the response of patients with colorectal tumors with the CpG island methylator phenotype (CIMP) to 5-FU–based therapy. Methods We analyzed a population-based cohort of 302 patients with colorectal cancer (CRC) for a median follow-up time of 50.7 months. CIMP status was determined by analysis of the CACNAG1 , SOCS1 , RUNX3 , NEUROG1 , and MLH1 promoters; tumors were considered to be CIMP positive if at least 3 promoters were methylated. Results Tumors from 29.5% of patients (89/302) were CIMP positive; CIMP status did not influence disease-free survival (DFS; log-rank = 0.3). Of tumors of TNM stages II–III (n = 196), 32.7% were CIMP positive. Among patients with stages II–III CRC who did not receive adjuvant 5-FU chemotherapy, those with CIMP-positive tumors had longest times of DFS (log-rank = 0.04); In patients who received chemotherapy, those with CIMP-positive tumors had shorter times of DFS (log-rank = 0.02). In patients with CIMP-negative tumors, adjuvant 5-FU chemotherapy significantly increased time of DFS (log-rank = 0.00001). However, in patients with CIMP-positive tumors, adjuvant 5-FU chemotherapy did not affect time of DFS (log-rank = 0.7). Multivariate analysis showed a significant, independent interaction between 5-FU treatment and CIMP status (hazard ratio [HR], 0.6; 95% confidence interval [CI], 0.5–0.8). Among patients with CIMP-positive tumors, adjuvant chemotherapy was not an independent predictor of outcome (HR, 0.8; 95% CI, 0.3–2.0). In patients who did not receive adjuvant 5-FU chemotherapy, CIMP status was the only independent predictor of survival (HR, 2.0; 95% CI, 1.1–3.8). Conclusions Patients with CIMP-positive colorectal tumors do not benefit from 5-FU–based adjuvant chemotherapy. |
| Databáze: | OpenAIRE |
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