Association of smoking with neutropenia and diarrhea in patients receiving irinotecan: A retrospective cohort study

Abstract

Aim: To evaluate the association between smoking status and irinotecan-related neutropenia and diarrhea, while exploring the potential impact of smoking intensity on these clinical outcomes.

Method: We conducted a retrospective cohort study of 58 patients receiving irinotecan-based chemotherapy, classified as active smokers (n=21) or non-smokers (n=37). The incidence and severity of neutropenia and diarrhea, along with granulocyte-colony stimulating factor (G-CSF) use, loperamide requirements, and treatment discontinuation rates, were compared between groups. An exploratory subgroup analysis was performed to assess the relationship between daily cigarette consumption and toxicity grades.

Results: In the primary analysis, no significant differences were found between smokers and non-smokers regarding neutropenia (p=0.430), diarrhea (p=0.921), G-CSF use (p=0.198), loperamide use (p=0.562), or treatment discontinuation (p=0.602). However, exploratory stratification by smoking quantity revealed a significant association with neutropenia patterns (p=0.014); higher cigarette consumption was correlated with a lower incidence of moderate-to-severe neutropenia. No significant correlation was observed between smoking quantity and diarrhea or other clinical endpoints.

Conclusion: While smoking status alone did not significantly affect irinotecan-related toxicities in this cohort, our findings suggest a dose-dependent relationship between smoking intensity and neutropenia. These results potentially reflect altered systemic exposure to the active metabolite SN-38. Given the retrospective nature and small subgroup sizes, these findings are hypothesis-generating and warrant validation in larger prospective trials incorporating pharmacokinetic and genetic data.