title: Pharmacokinetics and toxicity of weekly docetaxel in older patients.
abstract: 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.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York City, New York 10021, USA. hurriaa@mskcc.org
authors.forename: Arti
authors.initials: A
authors.lastname: Hurria
authors.forename: Mark T
authors.initials: MT
authors.lastname: Fleming
authors.forename: Sharyn D
authors.initials: SD
authors.lastname: Baker
authors.forename: Wm Kevin
authors.initials: WK
authors.lastname: Kelly
authors.forename: Katie
authors.initials: K
authors.lastname: Cutchall
authors.forename: Katherine
authors.initials: K
authors.lastname: Panageas
authors.forename: James
authors.initials: J
authors.lastname: Caravelli
authors.forename: Henry
authors.initials: H
authors.lastname: Yeung
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Jorge
authors.initials: J
authors.lastname: Gomez
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
mesh_terms: 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*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel