Pharmacokinetics and Pharmacogenetics of Metronomic Chemotherapy
Despite the numerous preclinical and clinical studies that have been conducted on metronomic chemotherapy in the past 10 years, few pharmacokinetic and pharmacogenetics data on this dosing regimen are available. Indeed, only the pharmacokinetics of metronomically administered drugs, such as irinotecan, UFT, and vinorelbine, have been described in patients, but no data are available on the most widely explored agents in such an approach like cyclophosphamide or capecitabine. Methodological issues and the neglected importance of the relationship between plasma concentrations of metronomically administered chemotherapeutic drugs (and their active metabolites) contributed to the absence of data on the commonly used 50 mg/day cyclophosphamide schedule. Moreover, few data are available on the pharmacogenetics of metronomic chemotherapy, and, although some objective responses have been obtained in various tumors, it remains largely unknown which genetic backgrounds could affect or predict the clinical response of patients. Trials integrating pharmacokinetic and pharmacogenetics research are necessary to better evaluate the clinical benefit of metronomic chemotherapy.