Originally published as JCO Early Release 10.1200/JCO.2005.03.9289 on March 27 2006

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Prospective Evaluation of the Relationship of Patient Age and Paclitaxel Clinical Pharmacology: Cancer and Leukemia Group B (CALGB 9762)

Stuart M. Lichtman, Donna Hollis, Antonius A. Miller, Gary L. Rosner, Chris A. Rhoades, Eric P. Lester, Frederick Millard, John Byrd, Stephen A. Cullinan, D. Marc Rosen, Robert A. Parise, Mark J. Ratain, Merrill J. Egorin

From the Cancer and Leukemia Group B; University of Chicago, Chicago; Illinois Oncology Research Assoc, Peoria, IL; North Shore University Hospital, New York University School of Medicine, Manhasset, NY; CALGB Statistical Center, Durham; Wake Forest University School of Medicine, Winston-Salem, NC; The Ohio State University Medical Center, Columbus, OH; University of California at San Diego, San Diego, CA; Walter Reed Army Medical Center, Washington, DC; University of Maryland Cancer Center, Baltimore, MD; University of Pittsburgh Cancer Institute and School of Medicine, Pittsburgh, PA.

Address reprint requests to Merrill J. Egorin, MD, University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Ave, G.27e, Pittsburgh, PA 15213; e-mail: egorinmj{at}msx.upmc.edu

PURPOSE: To prospectively evaluate the pharmacokinetics and toxicity profile of paclitaxel in relation to patient age in adults 55 years old.

PATIENTS AND METHODS: Paclitaxel was administered at 175 mg/m² for 3 hours to 153 patients, 46 of whom were 75 years of age. Pharmacokinetic and toxicity assessments were performed. Data were analyzed by cohort (cohort 1, age 55 to 64 years; cohort 2, age 65 to 74 years; cohort 3, age 75 years).

RESULTS: Paclitaxel concentration versus time (AUC) and total-body clearance (CL_tb) data were available for 122 patients (cohort 1, 46 patients; cohort 2, 44 patients; cohort 3, 32 patients). Mean paclitaxel AUC increased across cohorts (P = .01). Mean (SE) AUCs were 22.4 (2.5) µmol/L x hour, 26.2 (2.8) µmol/L x hour, and 31.7 (5.6) µmol/L x hour for cohorts 1, 2, and 3, respectively. There was a corresponding significant (P = .007) age-related decrease in mean (SE) paclitaxel CL_tb (cohort 1, 11.0 [0.7] L/h/m²; cohort 2, 9.3 [0.6] L/h/m²; cohort 3, 8.2 [0.6] L/h/m²). Patients in cohort 3 experienced significantly lower absolute neutrophil count nadirs than did younger groups (P = .02). There was also a significant increase in percentage of patients with grade 3 neutropenia across age cohorts (cohort 1, 22%; cohort 2, 35%; cohort 3, 49%; P = .006). However, the increased exposure of patients to paclitaxel and increased neutropenia were not reflected in adverse clinical sequelae such as hospitalization for toxicity (P = .82), receiving intravenous antibiotics (P = .21), or experiencing a temperature more than 38°C (P = .45).

CONCLUSION: Although paclitaxel CL_tb decreases with increasing patient age, there is great interpatient variability. Cooperative group studies to evaluate the effect of aging on pharmacokinetics are feasible.

Supported in part by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman).

Presented in part at the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12-15, 2001, and the 94th Annual Meeting of the American Association of Cancer Research, Washington, DC, July 11-14, 2003.

The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

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

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