In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 12 ( 2006-04-20), p. 1846-1851
Abstract:
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/m 2 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 × hour, 26.2 (2.8) μmol/L × hour, and 31.7 (5.6) μmol/L × 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/m 2 ; cohort 2, 9.3 [0.6] L/h/m 2 ; cohort 3, 8.2 [0.6] L/h/m 2 ). 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.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2005.03.9289
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2006
detail.hit.zdb_id:
2005181-5
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