CLINICALLY RELEVANT DRUG-DRUG INTERACTIONS IN ONCOLOGY

Although anticancer agents are one of the most toxic classes of medica tion prescribed today, there is relatively little information availabl e about clinically relevant drug-drug interactions. Pharmacokinetic dr ug interactions have been described, including alterations in absorpti on, catabolism, and excretion. For example, an increased bioavailabili ty of 6-mercaptopurine has been observed when combined with either all opurinol or methotrexate, leading to increased toxicity in some patien ts. Induction of etoposide or teniposide clearance by anticonvulsants has also been described, resulting in a lower systemic exposure and ri sk for lower anticancer activity. Alterations in elimination of methot rexate has been observed with probenecid, presumably through competiti on for renal secretion. There are also several examples of pharmacodyn amic interactions. The combination of 5-fluorouracil plus folinic acid results in more efficient inhibition of thymidylate synthase, a findi ng which is now utilized routinely in the treatment of colorectal canc er. Improvements in the in vitro and early clinical testing now allow a relatively high degree of prediction of potential clinical drug inte ractions, prior to observations of untoward drug effects. In conclusio n, drug interactions among commonly used anticancer agents have been i dentified. Their clinical significance can have more impact than many other classes of medications due to the narrow therapeutic index of an tineoplastic agents and the potential for lethal side-effects. It is o nly through prospective, preclinical and early clinical evaluation tha t the presence of clinically significant drug interactions can be iden tified and the information used to provide better therapy for this sig nificant health problem.