PURPOSE: To evaluate relationships between various body-size measures and irinotecan (CPT-11) clearance and metabolism in cancer patients, and to provide future dosing recommendations for this agent. PATIENTS AND METHODS: Pharmacokinetic data were obtained from 82 adult patients (50 men, 32 women; median age, 54 years) receiving CPT-11 as a 90-minute intravenous infusion (dose range, 175 to 350 mg/m(2)). In each patient, plasma samples were collected at timed intervals in the first administration of a 3-week schedule, and CPT-11 and its metabolite, SN-38, were measured by a liquid chromatographic assay. RESULTS: The mean (+/- SD) CPT-11 clearance was 33.6 +/- 10.8 L/h, with an interindividual variability (IIV) of 32.1%. When clearance was adjusted for body-surface area (BSA), the IIV was similar (34.0%). In addition, in a multiple linear regression analysis, none of the studied measures (BSA, lean body mass, [adjusted] ideal body weight, and body mass index) was a significant covariate (P >.13; r(2) <.014) in our population. Similarly, BSA did not significantly contribute to variability in the relative extent of conversion to SN-38 (P =.26). CONCLUSION: BSA is not a predictor of CPT-11 clearance or SN-38 pharmacokinetics and does not contribute to reducing kinetic variability. These findings provide a rationale for the conduct of a comparative phase III study between BSA-based dosing and flat or fixed dosing of CPT-11.
PURPOSE: To evaluate relationships between various body-size measures and irinotecan (CPT-11) clearance and metabolism in cancerpatients, and to provide future dosing recommendations for this agent. PATIENTS AND METHODS: Pharmacokinetic data were obtained from 82 adult patients (50 men, 32 women; median age, 54 years) receiving CPT-11 as a 90-minute intravenous infusion (dose range, 175 to 350 mg/m(2)). In each patient, plasma samples were collected at timed intervals in the first administration of a 3-week schedule, and CPT-11 and its metabolite, SN-38, were measured by a liquid chromatographic assay. RESULTS: The mean (+/- SD) CPT-11 clearance was 33.6 +/- 10.8 L/h, with an interindividual variability (IIV) of 32.1%. When clearance was adjusted for body-surface area (BSA), the IIV was similar (34.0%). In addition, in a multiple linear regression analysis, none of the studied measures (BSA, lean body mass, [adjusted] ideal body weight, and body mass index) was a significant covariate (P >.13; r(2) <.014) in our population. Similarly, BSA did not significantly contribute to variability in the relative extent of conversion to SN-38 (P =.26). CONCLUSION: BSA is not a predictor of CPT-11 clearance or SN-38 pharmacokinetics and does not contribute to reducing kinetic variability. These findings provide a rationale for the conduct of a comparative phase III study between BSA-based dosing and flat or fixed dosing of CPT-11.
Authors: Federico Innocenti; Richard L Schilsky; Jacqueline Ramírez; Linda Janisch; Samir Undevia; Larry K House; Soma Das; Kehua Wu; Michelle Turcich; Robert Marsh; Theodore Karrison; Michael L Maitland; Ravi Salgia; Mark J Ratain Journal: J Clin Oncol Date: 2014-06-23 Impact factor: 44.544
Authors: Vicki A Morrison; Linda McCall; Hyman B Muss; Aminah Jatoi; Harvey J Cohen; Constance T Cirrincione; Jennifer A Ligibel; Jacqueline M Lafky; Arti Hurria Journal: J Geriatr Oncol Date: 2017-12-08 Impact factor: 3.599
Authors: Kathryn M Field; Suzanne Kosmider; Michael Jefford; Michael Michael; Ross Jennens; Michael Green; Peter Gibbs Journal: J Oncol Pract Date: 2008-05 Impact factor: 3.840
Authors: Jessica M van der Bol; Floris A de Jong; Ron H van Schaik; Alex Sparreboom; Marianne A van Fessem; Fleur E van de Geijn; Paul L van Daele; Jaap Verweij; Stefan Sleijfer; Ron H Mathijssen Journal: Oncologist Date: 2010-10-07