PHARMACODYNAMIC MONITORING OF CANCER-CHEMOTHERAPY - CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA AS A MODEL

Childhood acute lymphoblastic leukemia (ALL) has long served as a mode l of disseminated cancer that can be cured with chemotherapy. Although pharmacokinetic variability has been shown to influence the efficacy of ALL chemotherapy, the usefulness of conventional pharmacokinetic me asures to predict responses to individual chemotherapeutic agents can be confounded in the context of multiagent chemotherapy. This has led to the concomitant use of pharmacodynamic endpoints to identify patien ts who exhibit a poor initial response to therapy or whose residual di sease has a persistence that predicts a poor prognosis unless therapy is changed. To this end, the initial reduction of leukemia cells in pe ripheral blood or in bone marrow and the detection of minimal residual disease by immunologic or polymerase chain reaction-based methods hav e shown promise as pharmacodynamic endpoints to identify patients who are at high risk for relapse if therapy remains unchanged. Prospective clinical trials are needed to determine the clinical usefulness of ph armacodynamic monitoring and to define more precisely the integration of pharmacokinetic and pharmacodynamic monitoring to optimize the trea tment of childhood ALL.