Drug Interactions in Cancer Therapy

Abstract and Introduction

Abstract

Drug interactions in oncology are of particular importance owing to the narrow therapeutic index and the inherent toxicity of anticancer agents. Interactions with other medications can cause small changes in the pharmacokinetics or pharmacodynamics of a chemotherapy agent that could significantly alter its efficacy or toxicity. Improvements in in vitro methods and early clinical testing have made the prediction of potentially clinically significant drug interactions possible. We outline the types of drug interaction that occur in oncology, the mechanisms that underlie these interactions and describe select examples.

Introduction

A drug interaction is defined as the pharmacological or clinical response to the administration or co-exposure of a drug with another substance that modifies the patient's response to the drug. It is reported that 20-30% of all adverse reactions to drugs are caused by interactions between drugs.^[1] This incidence increases among the elderly and patients who take two or more medications. Patients with cancer are particularly at risk of drug interactions as they could be taking many different medications as part of their cancer treatment or for the management of other illnesses. Examples of these types of interaction are shown ( Table 1 ) and discussed throughout this article.

Although the term 'drug interaction' usually has a negative connotation, it is important to note that drug interactions can have various outcomes. Interactions between drugs can increase or decrease the therapeutic or adverse response, or result in a unique response that does not occur when either agent is given alone.

The term 'drug interaction' is most often used to describe drug-drug interactions, but there are various substances and/or factors that can alter the pharmacokinetics and/or pharmacodynamics of medications. These include food,^[2] nutritional supplements,^[3] formulation excipients and environmental factors (such as cigarette smoking).^[4,5]

Drug interactions can occur throughout the process of drug disposition as a result of endogenous and exogenous factors (Fig. 1). Drug interactions can be the result of pharmacokinetic, pharmacodynamic or a combination of mechanisms. Pharmacokinetic interactions involve one drug or substance altering the absorption, distribution, metabolism or elimination of another drug or substance. A common example of a pharmacokinetic interaction occurs when two drugs compete for the same metabolic pathway. When the pathway becomes saturated neither drug can be metabolized fully, which results in higher serum concentrations of the agents and can lead to clinically unfavourable consequences. Pharmacodynamic interactions occur when two drugs or substances have similar molecular targets, but do not affect the pharmacokinetic parameters of each other. When two or more drugs that have similar pharmacodynamic activity are co-administered, the additive effects might result in an excessive response or toxicity. Pharmacodynamic interactions between drugs with opposing effects can reduce the response to one or both drugs.