In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 12 ( 2006-04-20), p. 1846-1851
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2005.03.9289
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2006
ZDB Id:
2005181-5
Permalink
