Smoking status affects chemotherapy-induced neutropenia

Abstract

8097 Background: A regimen of gemcitabine (G) and docetaxel (T) was tested concurrently in 39 patients with breast and 40 with lung cancer, and different toxicity profiles were observed. Multivariate analysis incorporating cancer type, gender, age and prior treatment showed that grade 4 neutropenia was seen more frequently among non-smokers, (p=0.03). Pharmacokinetic effect of smoking status on the clearance of both drugs was examined. G is cleared via renal excretion, and is affected by age and gender, but not by smoking status. T is metabolized by the enzyme cytochrome p450 3A4 (cyp 3A4), whose activity is not associated with smoking status, as demonstrated by measurement of erythromycin breath tests in a separate cohort of 79 sarcoma patients. Interactions between smoking and absolute neutrophil count (ANC) were investigated further. Methods: Charts of 466 patients treated with G and/or T in a single outpatient facility were reviewed. Cohorts were defined by drug dose and regimen. Within each cohort, mean ANC on cycle 1 day 8 was tested for association with smoking status and gender. Results: Compared to non-smokers, smokers had higher ANC after single agent G 800-1200/m2, or after G plus T 100/m2 (p=0.01),** but had lower ANC after single agent T 75 or 100/m2. Smokers treated with G plus T 75/m2 had higher ANC than did those treated with the same dose of T alone (p=0.01).* Gender had no effect on these observations. Conclusions: Smokers have higher ANC when treated with G, either alone or with T, but have lower ANC when treated with T alone. The addition of G to T in smokers results in improved ANC. These associations may be explained on the basis of the increased proliferation rate of myeloid progenitor cells, which has been reported in smokers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. Eli Lilly & Co.; Aventis