Therapeutic drug monitoring in oncology. Problems and potential in antineoplastic therapy

Abstract

Therapeutic drug monitoring is now widely used in many areas of medicine. With its proliferation has come an understanding of the clinical situations in which it is likely to be of value. Factors that can limit the usefulness of therapeutic drug monitoring and situations where it is less likely to be of benefit have also been identified. At present, the routine use of therapeutic drug monitoring in antineoplastic therapy is limited to measurement of plasma methotrexate concentrations after high-dose methotrexate therapy. The lack of a more widespread application of therapeutic drug monitoring in oncology has been due to deficiencies in knowledge about the clinical pharmacology of antineoplastic agents and to factors specific to the chemotherapy of neoplasms. These factors include the broad heterogeneity of malignant neoplasms, the complexities of the drug-tumour interaction, difficulties in assessment of this interaction and the use of combinations of antineoplastic agents with cumulative efficacies and toxicities. Despite these problems, there are many areas in antineoplastic therapy where the use of therapeutic drug monitoring could prove of benefit. The prevention of the chronic pulmonary toxicity of bleomycin, the assessment of the bioavailability of oral chemotherapy, and monitoring drug disposition in the presence of hepatic or renal dysfunction are just some of the potential applications. If recent emphasis on dose as a critical factor in the success of cancer chemotherapy is substantiated, then the need to apply therapeutic drug monitoring within oncology will become more pressing.