Pharmacokinetics and Toxicity of Weekly Docetaxel in Older Patients

• Published in: Clinical cancer research Vol. 12; no. 20; pp. 6100 - 6105
• Main Authors: Hurria, Arti, Fleming, Mark T, Baker, Sharyn D, Kelly, Wm Kevin, Cutchall, Katie, Panageas, Katherine, Caravelli, James, Yeung, Henry, Kris, Mark G, Gomez, Jorge, Miller, Vincent A, D'Andrea, Gabriella, Scher, Howard I, Norton, Larry, Hudis, Clifford
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.10.2006
• Subjects: Aged; Aging - drug effects; Antineoplastic agents; Antineoplastic Agents, Phytogenic - pharmacokinetics; Antineoplastic Agents, Phytogenic - toxicity; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; chemotherapy; docetaxel; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medical sciences; metastatic cancer; Neoplasm Metastasis; older patients; Pharmacology. Drug treatments; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Taxoids - pharmacokinetics; Taxoids - toxicity; Human; Antineoplastic agent; Toxicity; Taxane derivatives; Docetaxel; Pharmacokinetics; Antimitotic; Elderly
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-0200

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/m 2 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/m 2 starting dose. We advocate a starting dose of 26 mg/m 2 on this weekly schedule and dose escalating if no toxicity.