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 > 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.
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 > 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: C S Lancaster; G H Bruun; C J Peer; T S Mikkelsen; T J Corydon; A A Gibson; S Hu; S J Orwick; R H J Mathijssen; W D Figg; S D Baker; A Sparreboom Journal: Clin Pharmacol Ther Date: 2012-09-19 Impact factor: 6.875
Authors: Marie-Rose B S Crombag; Thomas P C Dorlo; Ellen van der Pan; Anoek van Straten; Andries M Bergman; Nielka P van Erp; Jos H Beijnen; Alwin D R Huitema Journal: Pharm Res Date: 2019-11-15 Impact factor: 4.200