title: Effects of cigarette smoking on metabolism and effectiveness of systemic therapy for lung cancer.
abstract: BACKGROUND
  Cigarette smoke associated polycyclic aromatic hydrocarbons can induce key drug-metabolizing enzymes of cytochrome P450 and isoforms of the glucuronyl transferases families. These enzymes metabolize several systemic therapies for lung cancer. Induction of these enzymes may lead to accelerated clearance with resultant impact on systemic therapy efficacy and toxicity in smokers compared with nonsmokers. This article reviews published literature regarding the influence of smoking as it relates to alteration of metabolism of systemic therapy in lung cancer.
  
  
  METHODS
  A structured search of the National Library of Medicine's PubMed/MEDLINE identified relevant articles. Data were abstracted and analyzed to summarize the findings.
  
  
  RESULTS
  Studies that analyzed pharmacokinetic data were prospective. Smokers receiving erlotinib exhibited rapid clearance, requiring a higher dose to reach equivalent systemic exposure compared with nonsmokers. Smokers receiving irinotecan also demonstrated increased clearance and lower systemic exposure. There was no difference in clearance of paclitaxel or docetaxel in smokers. Chemotherapy-associated neutropenia was worse in nonsmokers compared with smokers in patients treated with paclitaxel, docetaxel, irinotecan, and gemcitabine.
  
  
  CONCLUSIONS
  Systemic therapy for lung cancer has a narrow therapeutic index such that small changes in plasma concentrations or exposure in smokers may result in suboptimal therapy and poor outcomes. Smoking cessation must be emphasized at each clinical visit. However, prospective trials should take into consideration the effects of smoking history on drug pharmacokinetics and efficacy. The metabolizing enzyme phenotype in smokers may require individualized dose algorithms for specific agents.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Ann Arbor, MI.
authors.forename: Meaghan
authors.initials: M
authors.lastname: O'Malley
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Ann Arbor, MI.
authors.forename: Amanda N
authors.initials: AN
authors.lastname: King
authors.affiliation: Taubman Health Sciences Library, Ann Arbor, MI.
authors.forename: Marisa
authors.initials: M
authors.lastname: Conte
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor, MI.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Ellingrod
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Ann Arbor, MI; The Ann Arbor Veterans Administration Medical Center, Ann Arbor, MI. Electronic address: nithyar@umich.edu.
authors.forename: Nithya
authors.initials: N
authors.lastname: Ramnath
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077143:Docetaxel; D004790:Enzyme Induction / Q000187:drug effects*; D000069347:Erlotinib Hydrochloride; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D009503:Neutropenia / Q000209:etiology; D009538:Nicotine / Q000378:metabolism*; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000627:therapeutic use; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism; D011799:Quinazolines / Q000493:pharmacokinetics / Q000627:therapeutic use; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism; D043823:Taxoids / Q000493:pharmacokinetics / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D011084:Polycyclic Aromatic Hydrocarbons; D011799:Quinazolines; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D009538:Nicotine; D000077146:Irinotecan; D000069347:Erlotinib Hydrochloride; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D017239:Paclitaxel; D002166:Camptothecin; D000093542:Gemcitabine