Clinical pharmacokinetics of commonly used anticancer drugs

The quantitative aspects of drug disposition in man of the commonly used antineoplastic agents, including cyclophosphamide, the nitrosoureas, cisplatin, methotrexate, cytarabine, 5-fluorouracil, doxorubicin, daunorubicin, bleomycin, vincristine, vinblastine, and vindesine are reviewed. Although the pharmacokinetic behaviour of these drugs has been adequately described in man, the chemical reactivity, the complexity of metabolism and disposition, the lack of simple, rapid and sensitive assays to measure plasma concentration, and the lack of defined therapeutic and toxic plasma concentrations have limited the application of routine drug monitoring in clinical oncology. With the exception of high dose methotrexate, drug doses and administration schedules remain empirical with a standard starting dose and subsequent dosage modifications determined by ensuing drug toxicities. However, many of the pharmacological characteristics of the drugs, such as their low therapeutic index, potentially life-threatening toxicities and wide individual variability in drug disposition, necessitate pharmacological monitoring. Comprehensive pharmacokinetic analysis of new and established antineoplastic agents does play a role in defining dosage, administration schedule, route of administration, and dosage modification in the presence of organ dysfunction. Consideration of the kinetics of these drugs in planning treatment regimens could lead to more rational, safer and possibly more efficacious use.