Effects of tobacco smoking and nicotine on cancer treatment

Abstract

A substantial number of the world's population continues to smoke tobacco, even in the setting of a cancer diagnosis. Studies have shown that patients with cancer who have a history of smoking have a worse prognosis than nonsmokers. Modulation of several physiologic processes involved in drug disposition has been associated with long-term exposure to tobacco smoke. The most common of these processes can be categorized into the effects of smoking on cytochrome P450-mediated metabolism, glucuronidation, and protein binding. Perturbation in the pharmacokinetics of anticancer drugs could result in clinically significant consequences, as these drugs are among the most toxic, but potentially beneficial, pharmaceuticals prescribed. Unfortunately, the effect of tobacco smoking on drug disposition has been explored for only a few marketed anticancer drugs; thus, little prescribing information is available to guide clinicians on the vast majority of these agents. The carcinogenic properties of several compounds found in tobacco smoke have been well studied; however, relatively little attention has been given to the effects of nicotine itself on cancer growth. Data that identify nicotine's effect on cancer cell apoptosis, tumor angiogenesis, invasion, and metastasis are emerging. The implications of these data are still unclear but may lead to important questions regarding approaches to smoking cessation in patients with cancer.

Figure 1

Representative pharmacokinetic processes associated with tobacco smoking and their effects on drug disposition. CYP450 enzymes such as CYP1A1 (in lung) and glucuronosyltransferases such as UGT1A1 (in liver) are induced by exposure to tobacco smoke and lead to detoxification of parent drugs or active metabolites in the examples shown. Upregulation of alpha-1-acid glycoprotein (AAG) hepatic production as a result of inflammatory response to cancer and cigarette smoking results in increased protein bound drug and altered disposition.

Figure 2

Percent increase in mean serum AAG concentrations in smokers (n = 4,586) compared to nonsmokers (n = 1489). Adapted from Lind, et al.