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Medline ® Abstract for Reference 37

of 'The approach to ovarian cancer in older women'

37
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Prospective evaluation of the relationship of patient age and paclitaxel clinical pharmacology: Cancer and Leukemia Group B (CALGB 9762).
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Lichtman SM, Hollis D, Miller AA, Rosner GL, Rhoades CA, Lester EP, Millard F, Byrd J, Cullinan SA, Rosen DM, Parise RA, Ratain MJ, Egorin MJ, Cancer and Leukemia Group B (CALGB 9762)
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J Clin Oncol. 2006 Apr;24(12):1846-51. Epub 2006 Mar 27.
 
PURPOSE: To prospectively evaluate the pharmacokinetics and toxicity profile of paclitaxel in relation to patient age in adults>or = 55 years old.
PATIENTS AND METHODS: Paclitaxel was administered at 175 mg/m2 for 3 hours to 153 patients, 46 of whom were>or = 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>or = 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) micromol/L x hour, 26.2 (2.8) micromol/L x hour, and 31.7 (5.6) micromol/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>or = 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 degrees 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.
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University of Chicago, Chicago, USA.
PMID