Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatin.

  • Zaanan A
  • Cuilliere-Dartigues P
  • Guilloux A
 et al. 
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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.

Author-supplied keywords

  • Adenocarcinoma
  • Adenocarcinoma: drug therapy
  • Adenocarcinoma: genetics
  • Adenocarcinoma: metabolism
  • Adenocarcinoma: pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Antineoplastic Combined Chemotherapy Protocols: th
  • Colonic Neoplasms
  • Colonic Neoplasms: drug therapy
  • Colonic Neoplasms: genetics
  • Colonic Neoplasms: metabolism
  • Colonic Neoplasms: pathology
  • Disease-Free Survival
  • Female
  • Fluorouracil
  • Fluorouracil: administration & dosage
  • Humans
  • Leucovorin
  • Leucovorin: administration & dosage
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds
  • Organoplatinum Compounds: administration & dosage
  • Retrospective Studies
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Protein p53: metabolism
  • Tumor Suppressor Protein p53: physiology

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Authors

  • a Zaanan

  • P Cuilliere-Dartigues

  • a Guilloux

  • Y Parc

  • C Louvet

  • a de Gramont

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