A guide to clinically relevant drug interactions in oncology

Abstract

This paper presents an overview of new information on clinically relevant drug-drug interactions, particular focuses on negative drug interactions in oncology. We have generated a concise table of drug-drug interactions that provides a synopsis of the clinical outcome of the interaction along with a recommendation for management. We have also generated other tables that describe specific interactions with methotrexate and dosing guidelines for cytotoxic drugs in the presence of renal or hepatic dysfunction. Since warfarin is one of the non-anticancer drugs that is commonly used in cancer patients for the treatment and prevention of venous thromboembolism, its interactions with other anticancer drugs that have been reported in literatures were also reviewed in this paper. In general, drug interactions observed in cancer patients may be categorized into pharmacokinetic, pharmacodynamic and pharmaceutic interactions. Pharmacokinetic interactions involve one drug altering the absorption, distribution, metabolism, or excretion of another drug. Interpatient variability in the pharmacokinetic profile of many anticancer agents often complicates the predictability of the antitumor response and toxicities. Among four pharmacokinetic characteristics, drug interactions involving hepatic metabolism is probably the most common and important mechanism responsible for oncologic drug interactions. For example, several anticancer drugs including taxanes, vinca alkaloids, and irinotecan are known to be metabolized by cytochrome CYP3A4. Enzyme-inducing anticonvulsants have been shown to significantly decrease the plasma levels of these anticancer drugs, thereby compromising the anti-tumor effects. N ephrotoxicity or changes in hepatic function caused by some anticancer drugs (e.g., cisplatin, asparaginase) may also have an impact on the pharmacokinetics of the interacting agents. Pharmacodynamic interactions may occur when two or more drugs acting at a common receptor-binding site impact on the pharmacologic action of the object drug, without influencing the pharmacokinetics of each interacting agent. In clinical setting, a decrease of antitumor efficacy was observed in breast cell lines when gemcitabine or vinorelbine were used in combination with paclitaxel. On the other hand, a decreased incidence of thrombocytopenia was seen in patients receiving combination of carboplatin and palcitaxel compared to those receiving carboplatin alone. The third type of drug-drug interaction is known as pharmaceutic interaction. When one drug may alter the physical or chemical compatibility of another drug that utlimately leads to a change in appearance of the solution or a decrease of effectiveness of the drug due to drug inactivation or degradation.