[Pharmacodynamics of anticancer agents].
Studies of anticancer pharmacodynamics were reviewed. Pharmacodynamics deals with the relationship between therapeutic or toxic response and pharmacological measurements. It is suggested that the lack of pharmacodynamic information is currently limiting the application of pharmacokinetic information to cancer therapy. The studies contain pharmacodynamics of hematologic and non-hematologic toxicities, tumor response and cellular pharmacodynamics. It would be desirable to develop pharmacodynamic models using a limited sampling model during phase II trials, when all patients are treated with the same recommended dose, to relate pharmacokinetic parameters to tumor responses. The return knowledge of pharmacodynamics to cancer chemotherapy makes the concept of individualized therapy, adaptive control strategy with feedback (ACF) and targeted systemic exposure strategy (TSES). St. Jude Children's Research Hospital is now performing a randomized prospective trial to evaluate the efficacy and toxicity of conventional dosages versus individualized therapy using TSES with ACF in Acute lymphocytic leukemia pulse therapy with high-dose methotrexate, teniposide, and cytarabine. It would be a good model for the establishment of oncological pharmacology-based optimal administration of anticancer drugs.
Division of Hematology-Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
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Ohtsu
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Sasaki
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013810:Therapeutic Equivalency
D000970:Antineoplastic Agents