This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Minami, H. Articles by Ogata, H. Search for Related Content PubMed PubMed Citation Articles by Minami, H. Articles by Ogata, H. Social Bookmarking                            What's this?

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

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

Address reprint requests to Hironobu Minami, MD, Division of Oncology/Hematology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan; e-mail: hminami{at}east.ncc.go.jp

PURPOSE: 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.

PATIENTS AND METHODS: 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/m² for elderly and non-elderly patients, respectively. All patients received 25 mg/m² of cisplatin. The pharmacokinetics and pharmacodynamics of docetaxel and cisplatin were compared in elderly and non-elderly patients.

RESULTS: 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%).

CONCLUSION: 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.

Supported in part by Grants-in-Aid from the Ministry of Health and Welfare for the 2nd-Term Comprehensive 10-Year Strategy for Cancer Control.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				T. R. Asmis, K. Ding, L. Seymour, F. A. Shepherd, N. B. Leighl, T. L. Winton, M. Whitehead, J. N. Spaans, B. C. Graham, and G. D. Goss Age and Comorbidity As Independent Prognostic Factors in the Treatment of Non-Small-Cell Lung Cancer: A Review of National Cancer Institute of Canada Clinical Trials Group Trials J. Clin. Oncol., January 1, 2008; 26(1): 54 - 59. [Abstract] [Full Text] [PDF]

				C. Gridelli, P. Maione, A. Illiano, F. V. Piantedosi, A. Favaretto, A. Bearz, S. F. Robbiati, V. Filipazzi, V. Lorusso, F. Carrozza, et al. Cisplatin Plus Gemcitabine or Vinorelbine for Elderly Patients With Advanced Non Small-Cell Lung Cancer: The MILES-2P Studies J. Clin. Oncol., October 10, 2007; 25(29): 4663 - 4669. [Abstract] [Full Text] [PDF]

				L. D. Lewis, A. A. Miller, G. L. Rosner, J. E. Dowell, M. Valdivieso, M. V. Relling, M. J. Egorin, R. R. Bies, D. R. Hollis, E. G. Levine, et al. A Comparison of the Pharmacokinetics and Pharmacodynamics of Docetaxel between African-American and Caucasian Cancer Patients: CALGB 9871 Clin. Cancer Res., June 1, 2007; 13(11): 3302 - 3311. [Abstract] [Full Text] [PDF]

				S. M. Lichtman, H. Wildiers, E. Chatelut, C. Steer, D. Budman, V. A. Morrison, B. Tranchand, I. Shapira, and M. Aapro International Society of Geriatric Oncology Chemotherapy Taskforce: Evaluation of Chemotherapy in Older Patients--An Analysis of the Medical Literature J. Clin. Oncol., May 10, 2007; 25(14): 1832 - 1843. [Abstract] [Full Text] [PDF]

				C. Gridelli, C. Langer, P. Maione, A. Rossi, and S. E. Schild Lung Cancer in the Elderly J. Clin. Oncol., May 10, 2007; 25(14): 1898 - 1907. [Abstract] [Full Text] [PDF]

				A. Hurria, M. T. Fleming, S. D. Baker, Wm. K. Kelly, K. Cutchall, K. Panageas, J. Caravelli, H. Yeung, M. G. Kris, J. Gomez, et al. Pharmacokinetics and toxicity of weekly docetaxel in older patients. Clin. Cancer Res., October 15, 2006; 12(20): 6100 - 6105. [Abstract] [Full Text] [PDF]

				A. J. ten Tije, J. Verweij, M. A. Carducci, W. Graveland, T. Rogers, T. Pronk, M.P. Verbruggen, F. Dawkins, and S. D. Baker Prospective Evaluation of the Pharmacokinetics and Toxicity Profile of Docetaxel in the Elderly J. Clin. Oncol., February 20, 2005; 23(6): 1070 - 1077. [Abstract] [Full Text] [PDF]