Potential applications of therapeutic drug monitoring in treatment of neoplastic disease by antineoplastic agents

Abstract

Therapeutic drug monitoring of antineoplastic agents must be considered in terms of cytotoxicity to stem cells and toxicity of normal tissues. The dose-limiting toxicity which is myelosuppression is believed to be a necessary effect for maximal antitumour effect. The areas in which therapeutic drug monitoring can play a role include: predicting patients at risk of toxicity, e.g. high dose methotrexate therapy; low bioavailability, e.g. oral 6-mercaptopurine; identifying patients at risk of treatment failure, e.g. methotrexate clearance in acute lymphoblastic leukemia. Although therapeutic drug monitoring is not clinically useful at present, the potential role it can play is illustrated for cytosine arabinoside, adriamycin and cyclophosphamide. Two problems encountered with drug monitoring of antineoplastic disease are tumour heterogeneity manifested by clonal, nutritional and physical characteristics and the common practice of combination chemotherapy. These problems must be addressed in order to make therapeutic drug monitoring a practical tool in cancer chemotherapy. Future applications of therapeutic drug monitoring will require more studies to define therapeutic ranges for single agents, patient-to-patient variation, course-to-course variation and the effects of drug combinations on pharmacokinetic profiles of the drugs used.