Optimizing chemotherapy dose and schedule by Norton-Simon mathematical modeling Journal Article
| Authors: | Traina, T. A.; Dugan, U.; Higgins, B.; Kolinsky, K.; Theodoulou, M.; Hudis, C. A.; Norton, L. |
| Article Title: | Optimizing chemotherapy dose and schedule by Norton-Simon mathematical modeling |
| Abstract: | Background: To hasten and improve anticancer drug development, we created a novel approach to generating and analyzing preclinical dose-scheduling data so as to optimize benefit-to-toxicity ratios. Methods: We applied mathematical methods based upon Norton-Simon growth kinetic modeling to tumor-volume data from breast cancer xenografts treated with capecitabine (Xeloda®, Roche) at the conventional schedule of 14 days of treatment followed by a 7-day rest (14-7). Results: The model predicted that 7 days of treatment followed by a 7-day rest (7-7) would be superior. Subsequent preclinical studies demonstrated that this biweekly capecitabine schedule allowed for safe delivery of higher daily doses, improved tumor response, and prolonged animal survival. Conclusions: We demonstrated that the application of Norton-Simon modeling to the design and analysis of preclinical data predicts an improved capecitabine dosing schedule in xenograft models. This method warrants further investigation and application in clinical drug development. © 2010 - IOS Press and the authors. All rights reserved. |
| Keywords: | cancer chemotherapy; cancer survival; controlled study; survival rate; overall survival; drug safety; nonhuman; drug approval; capecitabine; mouse; breast cancer; tumor volume; animal experiment; animal model; antineoplastic activity; mathematical model; drug dose escalation; drug research; xenograft; optimal drug dose; drug dose regimen; mathematical computing; process optimization; chemotherapy schedule; norton-simon; xeloda®; chemical reaction kinetics |
| Journal Title: | Breast Disease |
| Volume: | 31 |
| Issue: | 1 |
| ISSN: | 0888-6008 |
| Publisher: | IOS Press |
| Date Published: | 2010-01-01 |
| Start Page: | 7 |
| End Page: | 18 |
| Language: | English |
| DOI: | 10.3233/bd-2009-0290 |
| PROVIDER: | scopus |
| PMCID: | PMC3228251 |
| PUBMED: | 20519801 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: BRDIE" - "Source: Scopus" |
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