Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation

Background: To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). Method: A retrospective study was performed in 124 consecutive patients with clinically T3N0-2M0-staged rectal cancer incorporating targeted agents in CCRT. Results: Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, p<0.0001), as evaluated by morphologic grading of hepatic steatosis and sinusoidal dilatation in laparoscopy. In the 57 patients with morphologically severe liver toxicity, 36 (63.2%) retained a normal liver function; for the remaining 21 patients with an abnormal liver function, the abnormality was self-limited in 19 patients, whereas 2 cetuximab-treated patients progressed to hepatic failure and mortality. A subset analysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes. Conclusions: The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for T3N0-2M0-staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.