Retrospective data suggests that tobacco smoking might increasethe clearance of irinotecan and reduce its toxicity,and presumably therefore, its efficacy.
In a retrospective analysis, pharmacokinetics of irinotecan were compared between 49 patients who were smokers and 141 who were nonsmokers, and who had received intravenous irinotecan 175 to 350 mg/m(See reference number 2)(or a fixed dose of 600 mg) once every 3 weeks. Clearance of irinotecan was 18 % faster in group of patients who smoked, and these patients also showed more extensive conversion of active metabolite SN-38 to inactive glucuronide (SN-38G). Smokers experienced significantly less haematological toxicity than non-smokers (grade 3 to 4 neutropenia 6 % versus 38%), possibly as a result of increased rate of clearance (See reference number 1).
Irinotecan is metabolised by cytochrome P450 CYP3A isoenzymes, which, although not most commonly implicated isoenzyme in interactions involving tobacco smoking, may be induced by some of components of tobacco smoke, resulting in increased clearance of irinotecan. In addition,smoking might induce glucuronyltransferases (which are responsible for glucuronidation) (See reference number 1).
The findings of this retrospective analysis suggest that smoking might reduce efficacy of irinotecan. However, evidence is insufficient to make recommendations regarding smoking cessation or an increased irinotecan dose (See reference number 1). Further study is required.
1. van der Bol JM,Mathijssen RHJ, Loos WJ, Friberg LE, van Schaik RHN, de Jonge MJA,Planting AST, Verweij J, Sparreboom A, de Jong FA. Cigarette smoking and irinotecan treatment: pharmacokinetic interaction and effects on neutropenia. J Clin Oncol (2007) 25. Published ahead of print at http://jco.ascopubs.org/cgi/reprint/JCO.2006.09.6115v1.