Pharmacokinetics and toxicity of weekly docetaxel in older patients.
OBJECTIVE
To evaluate the pharmacokinetics of weekly docetaxel in a cohort of older patients with metastatic cancer and to explore the relationship of pharmacokinetic variables, Erythromycin Breath Test results, age, geriatric assessment variables, and toxicity to therapy.


METHODS
Twenty patients ages > or = 65 years with metastatic breast, prostate, or lung cancer entered an Institutional Review Board-approved protocol to evaluate the pharmacokinetics of weekly docetaxel administered at 35 mg/m2 i.v. for 3 weeks followed by a 1-week break. The Erythromycin Breath Test and geriatric assessment were done before the first dose. Blood samples were collected for pharmacokinetic analysis with the first dose of docetaxel.


RESULTS
Of the 20 patients who entered the study, 19 were evaluable. There were no age-related differences in the pharmacokinetics of weekly docetaxel. Fifty-eight percent (11 of 19) experienced grade > or = 3 toxicity: 16% (3 of 19) grade > or = 3 hematologic toxicity, and 53% (10 of 19) grade > or = 3 nonhematologic toxicity. There was an association between the Erythromycin Breath Test results and docetaxel pharmacokinetic variables; however, there was no association between Erythromycin Breath Test results or docetaxel pharmacokinetics with frequency of grade > or = 3 toxicity.


CONCLUSIONS
Despite no statistically significant age-related differences in weekly docetaxel pharmacokinetics, over half of these older patients experienced a grade > or = 3 toxicity at the 35 mg/m2 starting dose. We advocate a starting dose of 26 mg/m2 on this weekly schedule and dose escalating if no toxicity.
Hurria
Arti
A
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York City, New York 10021, USA. hurriaa@mskcc.org
Fleming
Mark T
MT
Baker
Sharyn D
SD
Kelly
Wm Kevin
WK
Cutchall
Katie
K
Panageas
Katherine
K
Caravelli
James
J
Yeung
Henry
H
Kris
Mark G
MG
Gomez
Jorge
J
Miller
Vincent A
VA
D'Andrea
Gabriella
G
Scher
Howard I
HI
Norton
Larry
L
Hudis
Clifford
C
D000368:Aged; D000375:Aging / Q000187:drug effects*; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000493:pharmacokinetics* / Q000633:toxicity*
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel