Although acute nonlymphocytic leukemia and small cell lung cancer are malignancies in which a high percentage of complete remissions can be achieved with aggressive, multi-agent combination chemotherapy, studies at the University of Maryland Cancer Center and other institutions have shown that older patients suffer from increased toxicities and achieve complete remissions less frequently than do younger patients treated with the same combination chemotherapy. The basis for this difference is undefined and it is the objective of this proposal to investigate altered drug metabolism and disposition as a potential explanation for the enhanced toxicity and decreased complete remission rate observed in elderly patients treated at the University of Maryland Cancer Center. Prior to treatment with antineoplastic chemotherapy, patients will have their hepatic and renal drug metabolizing and excretory status assessed with liver function tests, indocyanine green clearance, antipydine clearance, and creatinine clearance. The plasma pharmacokinetics and metabolism of the antineoplastic agents administered to each patient will then be assessed. The data will then be analyzed for age-related alterations in renal and hepatic and renal function and alterations in each antineoplastic agent's pharmacokinetics and metabolism, for potiential age related drug-drug interactions not related to pretreatment hepatic and renal function, and finally for relationship between pharmacokinetics and the subsequently observed clinical effects. Any relationships observed, if translated into enhanced toxicity, or decreased complete remission rates will then serve as a basis for generation of dosage modifications based on age or hepatic or renal function.
