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

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.