Flat-fixed dosing of irinotecan: influence on pharmacokinetic and pharmacodynamic variability

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Floris A de JongAlex Sparreboom

Abstract

In a previous analysis, it was shown that body-surface area (BSA) is not a predictor of irinotecan pharmacokinetic parameters. Here, we prospectively evaluated the effects of administering a flat-fixed irinotecan dose to cancer patients, regardless of BSA. Twenty-six cancer patients (12 females) received a fixed irinotecan dose of 600 mg, given as a 90-min i.v. infusion. Plasma concentrations of irinotecan and its metabolites SN-38 (7-ethyl-10-hydroxycamptothecin) and SN-38G (SN-38 glucuronide) were measured during the first cycle and analyzed using nonlinear mixed-effect modeling. Data were compared with those obtained in 47 cancer patients (19 females) who received irinotecan at a BSA-normalized dose of 350 mg/m(2). The interindividual variability in irinotecan clearance (25.9% versus 25.1%; P = 0.93), in relative extent of conversion to SN-38 (47.8% versus 42.7%; P = 0.24), and in relative extent of SN-38 glucuronidation (71.2% versus 72.4%; P = 0.95) were not significantly different between the two dose groups. Variance differences in irinotecan-mediated hematological side effects were also similar between the 600 mg and 350 mg/m(2) groups (P > 0.14). These findings suggest that flat-fixed dosing of irinotecan does not resu...Continue Reading

References

Jul 17, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H P GurneyG Farrell
Aug 11, 1998·Journal of Chromatography. B, Biomedical Sciences and Applications·A SparreboomK Nooter
Sep 28, 1998·Cancer Chemotherapy and Pharmacology·M J Egorin
Jan 7, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M J de JongeJ Verweij
Aug 11, 2000·Paediatric Drugs·B J Anderson, J F Ellis
Sep 28, 2000·The New England Journal of Medicine·L B SaltzL L Miller
Mar 7, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·U VanhoeferY M Rustum
Jan 5, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark J Ratain
Apr 16, 2002·British Journal of Cancer·Howard Gurney
May 7, 2002·The Pharmacogenomics Journal·L IyerM J Ratain
Aug 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rujia XieMats O Karlsson
Nov 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric RaymondJean-Pierre Armand
Mar 29, 2003·BMJ : British Medical Journal·Katja Taxis, Nick Barber
Mar 10, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Federico InnocentiMark J Ratain

❮ Previous
Next ❯

Citations

Dec 22, 2004·Current Oncology Reports·Maurie Markman
May 2, 2006·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Vicente Valentí MorenoJosep Gumà Padró
May 17, 2013·Journal of Human Genetics·Daniel L Hertz, Howard L McLeod
Nov 4, 2004·Journal of the National Cancer Institute·Ron H J MathijssenAlex Sparreboom
Apr 8, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Federico InnocentiMark J Ratain
Oct 12, 2010·The Oncologist·Jessica M van der BolRon H Mathijssen
May 27, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Na GuoPeng Yu
Dec 2, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mo ZhouBohua Zhong
Sep 19, 2008·Expert Opinion on Drug Metabolism & Toxicology·Bo GaoHoward Gurney
Oct 2, 2007·Current Problems in Cancer·Russell P Kruzelock, William Short
Feb 20, 2007·Clinical Oncology : a Journal of the Royal College of Radiologists·S A Kaestner, G J Sewell
Feb 22, 2008·Clinical Pharmacology and Therapeutics·F A de JongJ Verweij
Jul 20, 2010·Chemico-biological Interactions·Renata KontekBeata Marciniak
Dec 14, 2005·Cancer Letters·Floris A de JongRon H J Mathijssen
Nov 8, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Nicola F SmithAlex Sparreboom
Jan 11, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jessica M van der BolRon H J Mathijssen
Apr 5, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jennifer J GriggsUNKNOWN American Society of Clinical Oncology
Jun 15, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jessica M van der BolFloris A de Jong
Jun 25, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mitch A Phelps, Alex Sparreboom
Feb 6, 2009·The Annals of Pharmacotherapy·David CzockFrieder Keller
Dec 23, 2006·Clinical Pharmacology and Therapeutics·F A de JongA Sparreboom
Aug 30, 2012·British Journal of Cancer·E ChatelutA Sparreboom
Apr 5, 2007·The Oncologist·Frederike K EngelsRon H J Mathijssen
Nov 26, 2015·World Journal of Gastroenterology : WJG·Ken-ichi FujitaYasutsuna Sasaki
Oct 30, 2020·Clinical Pharmacology and Therapeutics·Femke M de ManRon H J Mathijssen
Jul 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Linda E BrökerPatricia M Lorusso
Jan 14, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mark J Ratain, Federico Innocenti
Jan 14, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jessica M van der BolFloris A de Jong
Sep 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Floris A de JongHoward L McLeod

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Related Papers

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Ron H J MathijssenAlex Sparreboom
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Floris A de JongHoward L McLeod
Lancet
Joseph F Pizzolato, Leonard B Saltz
The New England Journal of Medicine
William E Evans, Howard L McLeod
© 2022 Meta ULC. All rights reserved