| Impact of body-size measures on irinotecan clearance: alternative dosing recommendations. | |
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MedLine Citation:
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PMID: 11773157 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ron H J Mathijssen; Jaap Verweij; Maja J A de Jonge; Kees Nooter; Gerrit Stoter; Alex Sparreboom |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology Volume: 20 ISSN: 0732-183X ISO Abbreviation: J. Clin. Oncol. Publication Date: 2002 Jan |
Date Detail:
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Created Date: 2002-01-04 Completed Date: 2002-02-01 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 8309333 Medline TA: J Clin Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 81-7 Citation Subset: IM |
Affiliation:
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Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek), 3008 AE Rotterdam, the Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Antineoplastic Agents, Phytogenic / administration & dosage*, pharmacokinetics* Body Constitution* Body Surface Area Camptothecin / administration & dosage*, analogs & derivatives*, pharmacokinetics* Colorectal Neoplasms / drug therapy Dose-Response Relationship, Drug Female Humans Infusions, Intravenous Linear Models Male Metabolic Clearance Rate Middle Aged Multivariate Analysis Netherlands Retrospective Studies |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 100286-90-6/irinotecan; 7689-03-4/Camptothecin |
| Comments/Corrections | |
Comment In:
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J Clin Oncol. 2002 Jan 1;20(1):7-8
[PMID:
11773147
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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