TP53 mutations in advanced colorectal cancer: The dark side of the moon

Filippo Pietrantonio, Pamela Biondani, Federica Perrone, Maria Di Bartolomeo, Monica Pacifici, Massimo Milione, Flavia Melotti, Claudia Maggi, Gabriella Montemurro, Ilaria Bossi, Luigi Mariani, Filippo De Braud

Research output: Contribution to journalArticle

Abstract

Background: Evidence for TP53 mutations as biomarker in colorectal cancer (CRC) is conflicting. Methods: We assessed TP53 mutations in 51 patients with advanced CRC enrolled into a phase II, randomised trial of first-line tegafur-uracil (UFT)/leucovorin (LV) plus irinotecan (n = 23) versus UFT/LV plus oxaliplatin (n = 28). Results: Non-functional TP53 mutations were found in 35% of patients. The response rate was not significantly different according to TP53 status. Progression-free and overall survival were longer in patients with TP53 mutations compared to those with wild-type TP53 (9 vs. 6.5 months, p = 0.0504, and 39.2 vs. 19.6 months, p = 0.0055, respectively). On multivariable analysis, TP53 mutation was independently associated with a decreased risk of death (hazard ratio 0.329, 95% CI 0.159-0.679; p = 0.0026). Treatment arm did not interact with TP53 in influencing outcomes. Conclusion:TP53 was not predictive of benefit from first-line irinotecan- or oxaliplatin-based chemotherapy. TP53 mutations may possibly be associated with a more indolent course of CRC after the diagnosis of metastatic disease.

Original languageEnglish
Pages (from-to)289-294
Number of pages6
JournalOncology
Volume86
Issue number5-6
DOIs
Publication statusPublished - 2014

Keywords

  • Biomarker
  • Chemotherapy
  • Colorectal cancer
  • p53
  • Prognosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Pietrantonio, F., Biondani, P., Perrone, F., Di Bartolomeo, M., Pacifici, M., Milione, M., Melotti, F., Maggi, C., Montemurro, G., Bossi, I., Mariani, L., & De Braud, F. (2014). TP53 mutations in advanced colorectal cancer: The dark side of the moon. Oncology, 86(5-6), 289-294. https://doi.org/10.1159/000360088