MAKING TDM WORK TO OPTIMIZE CANCER-CHEMOTHERAPY - A MULTIDISCIPLINARYTEAM-APPROACH

Several factors can limit the use of therapeutic drug monitoring (TDM) for cancer chemotherapeutic agents, including poorly defined concentr ation-effect relationships for many antineoplastic agents. This is fur ther complicated by cancer being a highly heterogeneous group of disea ses, each Of which may have a unique concentration-effect relationship for any given drug or drug combination. Nonetheless, TDM clearly has the potential to improve the clinical use of antineoplastic agents, mo st of which have very narrow therapeutic indices and highly variable p harmacokinetics. A substantial body of literature accumulating during the past 15 years demonstrates relationships between systemic exposure to various anticancer drugs and their toxic oz therapeutic effects. T his review selected highlights studies that illustrate concentration-e ffect relationship for the antineoplastic effects of 5-fluorouracil, m ercaptopurine, and methotrexate. A much larger number of pharmacodynam ic studies have established the relationship between serum concentrati on and dose-limiting toxicities for anticancer agents, Including epipo dophylotoxins, platinum compounds camptothecin, anthracyclines, and an timetabolites, In this review we will focus on anticancer drugs for wh ich the pharmacodynamics of antineoplastic effects have been elucidate d. We will also address issues critical to the optimal use of TDM in a clinical setting, which requires effective participation by a multidi sciplinary team of professionals.