Cigarette smoking during irinotecan therapy: Effects on pharmacokinetics and neutropenia
Cytochrome P450 enzymes in the liver are important for the detoxification of many drugs and substances. Exposure to cigarette smoke can affect the expression of cytochrome P450 enzymes and has been demonstrated to affect the levels and clearance of a number of different medications. The study used a retrospective analysis (looking back over records) to explore the effects of smoking on the blood levels of irinotecan and the substance it is broken down into, SN-38, as well as the risk of toxicities.
Of the 202 patients, 49 were identified as smokers (26%) and 141 as non-smokers (74%). Smokers had lower blood levels of irinotecan and SN-38, which resulted in lower rates of side effects. Low white blood cell count was seen in 9% of smokers vs. 32% of non smokers and neutropenia (low neutrophil count) in 6% of smokers compared to 38% of non smokers. Given the lower exposure to irinotecan and SN-38 and the lower incidence of exposure-related toxicity, it seems reasonable to hypothesize that smoking has a negative effect of the efficacy of irinotecan by effectively decreasing the dose in the body.
Further investigation with regards to the effect of cigarette smoking on survival outcomes in patients treated with this drug would be interesting; however, the authors were unable to perform the necessary analyses to answer this question. The effect of cigarette smoking on the metabolism of other chemotherapies would be interesting; however, because there are so many different variables (age, race, gender, genetic polymorphisms, and concurrent medication usage), the importance of cigarette smoking in patients receiving cancer treatment may never be fully understood.