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Clinical pharmacology of paclitaxel in relation of patient age: CALGB 9762

Li Liu, MD

University of Pennsylvania Cancer
Last Modified: May 13, 2001

Presenter: S.M. Lichtman
Affiliation: CALGB, Chicago, IL

Background:

The taxanes are one of the most important new classes of anticancer agents to emerge in the last decade. Paclitaxel, one of the two taxanes, has been widely used in patients with various malignancies, especially in the elderly population. However, its pharmacokinetics and pharmacodynamics among elderly population have not been established.

Materials and Methods:

• A total of 148 patients, age 55 years or older, with various non
• hematologic malignancies were included in this prospective study
• Total body Clearance (TBC) and toxicity of paclitaxel were evaluated
• None of the patients received paclitaxel previously
• There were 3 patient cohorts: 55
• 64 years, 65
• 74 years, and 75 years and older

Results:

• Age is a significant factor in total body clearance, AUC, and decline in WBC nadir
• The decline in absolute neutrophil count was not statistically significantly associated with age
• Age is significantly associated with grade 3 ANC toxicity

Authors' Conclusions

• There is decreased paclitaxel clearance with age
• There is increased myelosuppression with age

Clinical/Scientific Implications:

• There is significant interpatient variability in paclitaxel clearance and age related changes account for only of modest proportion
• Clinical trials evaluating the effects of aging on pharmacology of anticancer in cooperative trials are feasible