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Medline ® Abstract for Reference 37

of 'The approach to ovarian cancer in older women'

Prospective evaluation of the relationship of patient age and paclitaxel clinical pharmacology: Cancer and Leukemia Group B (CALGB 9762).
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)
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.
University of Chicago, Chicago, USA.