TY - JOUR
T1 - Prospective evaluation of the relationship of patient age and paclitaxel clinical pharmacology
T2 - Cancer and Leukemia Group B (CALGB 9762)
AU - Lichtman, Stuart M.
AU - Hollis, Donna
AU - Miller, Antonius A.
AU - Rosner, Gary L.
AU - Rhoades, Chris A.
AU - Lester, Eric P.
AU - Millard, Frederick
AU - Byrd, John
AU - Cullinan, Stephen A.
AU - Rosen, D. Marc
AU - Parise, Robert A.
AU - Ratain, Mark J.
AU - Egorin, Merrill J.
PY - 2006/4/20
Y1 - 2006/4/20
N2 - 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 (CLtb) 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 CLtb (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 CLtb decreases with increasing patient age, there is great interpatient variability. Cooperative group studies to evaluate the effect of aging on pharmacokinetics are feasible.
AB - 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 (CLtb) 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 CLtb (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 CLtb 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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U2 - 10.1200/JCO.2005.03.9289
DO - 10.1200/JCO.2005.03.9289
M3 - Article
C2 - 16567769
AN - SCOPUS:33646366957
SN - 0732-183X
VL - 24
SP - 1846
EP - 1851
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 12
ER -