Lack of Bax expression is associated with irinotecan-based treatment activity in advanced colorectal cancer patients

Clin Transl Oncol. 2013 Jul;15(7):582-6. doi: 10.1007/s12094-012-0971-3. Epub 2012 Nov 21.

Abstract

Background: Currently, first-line chemotherapy in advanced colorectal cancer is not tailored on predictive biomarkers. Bax proapoptotic protein may correlate to chemosensitivity and differential response to irinotecan or oxaliplatin-based combinations.

Methods: Bax expression was assessed by immunohistochemistry in 49 advanced colorectal cancer patients enrolled at our institution from 2002 to 2004 within a multicenter, phase II, randomized trial of first-line UFT/leucovorin/irinotecan (TEGAFIRI) versus UFT/leucovorin/oxaliplatin (TEGAFOX).

Results: Bax-positive and negative samples were 49 and 51 %. Response was significantly lower in Bax positive (25 %) as compared to Bax negative (56 %) (Odds ratio = 0.26; p = 0.03). No significant difference was noted in TEGAFOX subgroup; in TEGAFIRI arm, responses were lower in Bax positive (18 %) than Bax negative (67 %) (Odds ratio = 0.11; p = 0.03). No difference in terms of progression-free and overall survival was observed according to Bax.

Conclusion: Bax-negative colorectal cancer may identify a specific phenotype of patients with significantly higher chance to respond to doublet irinotecan-based chemotherapy.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Irinotecan
  • Leucovorin / administration & dosage
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Antineoplastic Agents
  • bcl-2-Associated X Protein
  • Irinotecan
  • Leucovorin
  • Camptothecin