628 - Prognostic role of ERCC1, BAX and TP53 in advanced colorectal cancer (CRC) pts randomly assigned to first-line UFT/leucovorin (LV) plus irinotecan (...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Translational Research
Presenter Filippo Pietrantonio
Authors F. Pietrantonio1, P. Biondani1, M. Milione2, F. Perrone2, F.G.M. De Braud1, G. Bertarelli3, L. Mariani3, F. Melotti2, G. Montemurro2, M. Di Bartolomeo1
  • 1Oncologia Medica 1, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 2Pathology Department, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano,, 20133 - Milan/IT
  • 3Medical Statistics, Biometry, And Bioinformatics, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano, 20133 - Milan/IT

Abstract

Background

Currently, no validated biomarkers are available to tailor first-line chemotherapy in advanced CRC. In particular, Bax expression may be related to chemosensitivity, although Bax-negative CRC may display higher responses to irinotecan (Fallik et al, Cancer Res 2003). Candidate apoptosis-related biomarkers were assessed in patients enrolled into a multicenter, phase II, randomized trial of TEGAFIRI vs TEGAFOX (Bajetta et al, Br J Cancer 2007).

Methods

Tissue blocks were available for a subset of 49 pts who provided written consent and were enrolled from August 2002 to October 2004 at the coordinator center “Istituto Nazionale dei Tumori” of Milan. ERCC1, Bax and TP53 expression assessed by immunohistochemistry, with dicotomic discrimination. Association with RECIST response by logistic univariate regression and corrected Chi square test; interaction of significant biomarkers and treatment arm by logistic regression model. Progression-free (PFS) and overall survival (OS) curves were plotted by the Kaplan-Meier method and compared by log-rank test. Correlation with PFS and OS by univariate and multivariate Cox's proportional hazard model.

Results

Overall, 41% response rate (20/49, 4 CR/16 PR/19 SD/10 PD). ERCC1 and TP53 failed to show any correlation with outcome. Responses significantly lower in Bax-positive vs Bax-negative (Odds Ratio [OR] = 0.26; p = 0.03 by logistic regression): 25% (6/24) vs 56% (14/25) (p = 0.05 by Chi square). No significant differences in terms of outcome in TEGAFOX-treated pts, while Bax-positive pts in TEGAFIRI subgroup had lower response rate as compared to Bax-negative (OR = 0.11; p = 0.03 by logistic regression): 18% (8/12) vs 67% (2/11) (p = 0.05 by Chi square). In the overall population and both treatment subgroups, no significant differences in terms of PFS and OS according to selected biomarkers. Data on TP53 gene sequencing by means of polymerase-chain reaction will be presented at the Congress.

Conclusion

Doublet UFT-based chemotherapy and, in particular, irinotecan-based treatment produced higher response rates in Bax-negative advanced CRC. Further prospective evaluation of Bax in patients undergoing triplet chemotherapy and anti-EGFR containing regimens is warranted.

Disclosure

All authors have declared no conflicts of interest.