Cigarettes smoking habit may reduce benefit from cetuximab-based treatment in advanced colorectal cancer patients

NF-kappaB is one of the nuclear effectors of EGFR activation. There are reports showing that NF-kappaB expression and activity is enhanced after nicotine treatment. Some data demonstrated that NF-kappaB activation plays a role in the induction of resistance to cetuximab and irinotecan in advanced colorectal tumors. The aim of this study was to evaluate the effect of cigarette smoking on cetuximab efficacy in advanced colorectal cancer patients.

We retrospectively analysed the smoking habits of 200 patients treated with a variety of anticancer regimens containing cetuximab for advanced colorectal cancer. All patients were irinotecan-resistant and received an oxaliplatin-based first line treatment. We divided our patient population as follows: no previous smoking habit, previous smokers (any number of cigarettes), current smokers of less of 10 cigarettes/day, current smokers of more than 10 cigarettes/day.

Out of 200 patients 58 declared a history of cigarette smoking, 108 patients never smoked and the remaining 44 patients were cigarette smokers during cetuximab-based anticancer therapy. Of the 44 smokers, 18 smoked more than 10 cigarettes per day. No statistically significant differences in terms of response rate (RR) and time to progression (TTP) were identified between previous smokers and never smokers. RR in actual smokers was 13.6% and was lower than RR reported for non-smokers (27.1%; p = 0.023). In addition, the median TTP was 5.5 months in the non-smokers versus 2.8 months in the current smokers (p < 0.0001). A difference in terms of overall survival (OS) was detected between the two groups (p = 0.03). Comparing smokers of more than 10 cigarettes per day and smokers of less than 10 cigarettes per day no differences were detected in RR, TTP or OS.

Our results suggest that cigarette smoking during anticancer treatment with a cetuximab-based regimen may be responsible for a decrease in RR and lead to a lower TTP.