Pharmacokinetics and toxicity of weekly docetaxel in older patients Journal Article

Authors: Hurria, A.; Fleming, M. T.; Baker, S. D.; Kelly, Wm K.; Cutchall, K.; Panageas, K.; Caravelli, J.; Yeung, H.; Kris, M. G.; Gomez, J.; Miller, V. A.; D'Andrea, G.; Scher, H. I.; Norton, L.; Hudis, C.
Article Title: Pharmacokinetics and toxicity of weekly docetaxel in older patients
Abstract: Purpose: 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. Experimental Design: Twenty patients ages ≥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 ≥3 toxicity: 16% (3 of 19) grade ≥3 hematologic toxicity, and 53% (10 of 19) grade ≥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 ≥3 toxicity. Conclusions: Despite no statistically significant age-related differences in weekly docetaxel pharmacokinetics, over half of these older patients experienced a grade ≥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. © 2006 American Association for Cancer Research.
Keywords: cancer chemotherapy; clinical article; controlled study; treatment outcome; aged; disease course; fatigue; neutropenia; diarrhea; protein function; infection; neuropathy; lung neoplasms; antineoplastic agents, phytogenic; dexamethasone; breast neoplasms; docetaxel; dyspnea; prostate cancer; prostatic neoplasms; confusion; hypokalemia; lung metastasis; disease severity; drug distribution; blood analysis; neoplasm metastasis; drug clearance; aging; daily life activity; taxoids; drug metabolism; liver function test; drug half life; heart arrhythmia; aphasia; breast metastasis; drug dose regimen; hallucination; hematologic disease; geriatric assessment; hypocalcemia; erythromycin; cytochrome p450 3a4; breath analysis
Journal Title: Clinical Cancer Research
Volume: 12
Issue: 20
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2006-10-15
Start Page: 6100
End Page: 6105
Language: English
DOI: 10.1158/1078-0432.ccr-06-0200
PUBMED: 17062686
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 28" - "Export Date: 4 June 2012" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Jorge Gomez
    26 Gomez
  2. Clifford Hudis
    848 Hudis
  3. Larry Norton
    581 Norton
  4. William K Kelly
    110 Kelly
  5. Henry W D Yeung
    127 Yeung
  6. Arti Hurria
    35 Hurria
  7. Vincent Miller
    263 Miller
  8. Katherine S Panageas
    331 Panageas
  9. Howard Scher
    835 Scher
  10. Mark Kris
    612 Kris