Comparison of Pharmacokinetics and Pharmacodynamics of Docetaxel and Cisplatin in Elderly and Non-Elderly Patients: Why Is Toxicity Increased in Elderly Patients?

DOI Web Site 被引用文献4件
  • Hironobu Minami
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Yuichi Ohe
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Seiji Niho
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Koichi Goto
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Hironobu Ohmatsu
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Kaoru Kubota
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Ryutaro Kakinuma
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Yutaka Nishiwaki
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Hiroshi Nokihara
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Ikuo Sekine
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Nagahiro Saijo
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Kazuhiko Hanada
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan
  • Hiroyasu Ogata
    From the Divisions of Oncology/Hematology and Thoracic Oncology, National Cancer Center Hospital East, Kashiwa; Division of Internal Medicine, National Cancer Center Hospital; Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan

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<jats:sec><jats:title>Purpose</jats:title><jats:p> Following phase I studies of docetaxel and cisplatin in patients with non–small-cell lung cancer, the recommended doses of docetaxel were different for elderly (≥ 75 years) and non-elderly (< 75 years) patients. To elucidate the mechanism of the difference, the pharmacokinetics of docetaxel and cisplatin were investigated in two phase II studies separately conducted in elderly and non-elderly patients. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> Twenty-seven elderly and 25 non-elderly patients were treated with three weekly administrations of docetaxel and cisplatin every 4 weeks. Doses of docetaxel were 20 and 35 mg/m<jats:sup>2</jats:sup> for elderly and non-elderly patients, respectively. All patients received 25 mg/m<jats:sup>2</jats:sup> of cisplatin. The pharmacokinetics and pharmacodynamics of docetaxel and cisplatin were compared in elderly and non-elderly patients. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> There were no differences in pharmacokinetics of docetaxel or cisplatin between elderly versus non-elderly patients with regard to clearance and volume of distribution. In the pharmacodynamic analysis, neutropenia was positively correlated with the area under the concentration-time curve for docetaxel but not for cisplatin. In evaluating the relationship between neutropenia and the area under the concentration-time curve of docetaxel, elderly patients experienced greater neutropenia than those predicted by a pharmacodynamic model developed in non-elderly patients; the residual for prediction of the percent change in neutrophil count was −11.2% (95% CI, −21.8 to −0.5%). </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> The pharmacokinetics of docetaxel and unchanged cisplatin were not different between elderly and non-elderly patients. The elderly patients were more sensitive to docetaxel exposure than the non-elderly patients, resulting in the different recommended doses for the phase II studies. </jats:p></jats:sec>

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