title: Factors affecting pharmacokinetic variability following doxorubicin and docetaxel-based therapy.
abstract: Current dosing strategies for anticancer drugs result in wide interindividual pharmacokinetic variability. Here, we explored the influence of age, body size, concomitant drugs, dose, infusion duration, and sex on the clearance for doxorubicin and docetaxel in 243 individual patients. Patients received doxorubicin (n=110) or docetaxel (n=152) as monotherapy or in combination chemotherapy regimens. The mean (+/-S.D.) clearance was 63.6+/-22.7 L/h for doxorubicin and 42.8+/-14.9 L/h for docetaxel. Normalisation for body surface area (BSA) reduced the interindividual variability by only <1.7%. Doxorubicin clearance was significantly reduced when administered at doses >50 mg/m(2) or in combination with cyclophosphamide. Upper extremes of body size were associated with increased clearance for both drugs, whereas no consistent effect of age on clearance was discerned. Overall, these findings suggest that incorporation of variables in addition to BSA should be considered in routine dosing strategies for doxorubicin and docetaxel.
authors.affiliation: Division of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231-1000, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Rudek
authors.forename: A
authors.initials: A
authors.lastname: Sparreboom
authors.forename: E S
authors.initials: ES
authors.lastname: Garrett-Mayer
authors.forename: D K
authors.initials: DK
authors.lastname: Armstrong
authors.forename: A C
authors.initials: AC
authors.lastname: Wolff
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.forename: S D
authors.initials: SD
authors.lastname: Baker
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001824:Body Constitution; D015992:Body Mass Index; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin