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.
TP53 mutations in advanced colorectal cancer : the dark side of the moon / F. Pietrantonio, P. Biondani, F. Perrone, M. Di Bartolomeo, M. Pacifici, M. Milione, F. Melotti, C. Maggi, G. Montemurro, I. Bossi, L. Mariani, F. De Braud. - In: ONCOLOGY. - ISSN 0030-2414. - 86:5-6(2014 Jul), pp. 289-294.
|Titolo:||TP53 mutations in advanced colorectal cancer : the dark side of the moon|
PIETRANTONIO, FILIPPO (Corresponding)
BIONDANI, PAMELA (Secondo)
DE BRAUD, FILIPPO GUGLIELMO MARIA (Ultimo)
|Parole Chiave:||Biomarker; Chemotherapy; Colorectal cancer; p53; Prognosis; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; DNA Mutational Analysis; Disease-Free Survival; Female; Genetic Association Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mutation; Neoplasm Staging; Proportional Hazards Models; Randomized Controlled Trials as Topic; Tumor Suppressor Protein p53; Cancer Research; Oncology|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||lug-2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1159/000360088|
|Appare nelle tipologie:||01 - Articolo su periodico|