Active smoking is associated with shorter survival in pancreatic cancer patients treated with neoadjuvant leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), according to research published in the European Journal of Cancer.

The median overall survival (OS) was about 2 years in active smokers treated with neoadjuvant FOLFIRINOX, but it was not reached in never smokers and former smokers who received the same treatment.

In this retrospective study, researchers analyzed data from 848 patients who underwent resection for pancreatic ductal adenocarcinoma (PDAC) during 2010-2020. About half of patients (54.7%) were never smokers, 29.5% were former smokers, and 15.8% were active smokers.  

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More patients underwent upfront resection (57.9%) than received neoadjuvant treatment (42.1%). The most common neoadjuvant treatment was FOLFIRINOX (58.8%).

At a median follow-up of 34.3 months, the median OS for all patients was 27.8 months. The median OS was 28.1 months in never smokers, 30.6 months in former smokers, and 20.7 months in active smokers (P =.19).

In a covariate-adjusted analysis, among patients who received neoadjuvant therapy, the predicted median OS was 44.7 months for never smokers, 40.0 months for former smokers, and 22.8 months for active smokers.

Among patients who received neoadjuvant FOLFIRINOX specifically, the predicted median OS was not yet reached in never smokers and former smokers but was 26.2 months in active smokers.

In an interaction analysis, neoadjuvant FOLFIRINOX and active smoking were associated with a significant increase in the risk of death (hazard ratio [HR], 2.63; 95% CI, 1.33-5.21). Neoadjuvant FOLFIRINOX and never smoking were associated with a significant decrease in the risk of death (HR, 0.40; 95% CI, 0.25-0.63), and neoadjuvant FOLFIRINOX and former smoking were associated with a nonsignificant decrease in the risk of death (HR, 0.58; 95% CI, 0.33-1.02).

“[T]his is the first study to provide evidence that active smoking impairs the excellent survival of neoadjuvant FOLFIRINOX therapy,” the researchers wrote. “Prospective studies in PDAC patients, conducted prior to the initiation of FOLFIRINOX treatment, are urgently needed to further investigate this association.”


Leonhardt C-S, Pils D, Qadan M, et al. Smoking impairs the effect of neoadjuvant FOLFIRINOX on postresection survival in pancreatic cancer. Eur J Cancer. Published online August 21, 2023. doi:10.1016/j.ejca.2023.113293