Predicting Approximate Clinically Effective Doses in Oncology Using Preclinical Efficacy and Body Surface Area Conversion: A Retrospective Analysis
The correlation between efficacious doses in human tumor-xenograft mouse models and the human clinical doses of approved oncology agents was assessed using published preclinical data and recommended clinical doses. For 90 approved small molecule anti-cancer drugs, body surface area (BSA) corrected m...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.830972/full |
| _version_ | 1828472751151644672 |
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| author | Robert J. Griffin Ethan Avery Cindy Q. Xia |
| author_facet | Robert J. Griffin Ethan Avery Cindy Q. Xia |
| author_sort | Robert J. Griffin |
| collection | DOAJ |
| description | The correlation between efficacious doses in human tumor-xenograft mouse models and the human clinical doses of approved oncology agents was assessed using published preclinical data and recommended clinical doses. For 90 approved small molecule anti-cancer drugs, body surface area (BSA) corrected mouse efficacious doses were strongly predictive of human clinical dose ranges with 85.6% of the predictions falling within three-fold (3×) of the recommended clinical doses and 63.3% within 2×. These results suggest that BSA conversion is a useful tool for estimating human doses of small molecule oncology agents from mouse xenograft models from the early discovery stage. However, the BSA based dose conversion poorly predicts for the intravenous antibody and antibody drug conjugate anti-cancer drugs. For antibody-based drugs, five out of 30 (16.7%) predicted doses were within 3× of the recommended clinical dose. The body weight-based dose projection was modestly predictive with 66.7% of drugs predicted within 3× of the recommended clinical dose. The correlation was slightly better in ADCs (77.7% in 3×). The application and limitations of such simple dose estimation methods in the early discovery stage and in the design of clinical trials are also discussed in this retrospective analysis. |
| first_indexed | 2024-12-11T05:34:24Z |
| format | Article |
| id | doaj.art-9b32fdea2b774d79a27e4cd5f09dcf25 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T05:34:24Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-9b32fdea2b774d79a27e4cd5f09dcf252022-12-22T01:19:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-04-011310.3389/fphar.2022.830972830972Predicting Approximate Clinically Effective Doses in Oncology Using Preclinical Efficacy and Body Surface Area Conversion: A Retrospective AnalysisRobert J. GriffinEthan AveryCindy Q. XiaThe correlation between efficacious doses in human tumor-xenograft mouse models and the human clinical doses of approved oncology agents was assessed using published preclinical data and recommended clinical doses. For 90 approved small molecule anti-cancer drugs, body surface area (BSA) corrected mouse efficacious doses were strongly predictive of human clinical dose ranges with 85.6% of the predictions falling within three-fold (3×) of the recommended clinical doses and 63.3% within 2×. These results suggest that BSA conversion is a useful tool for estimating human doses of small molecule oncology agents from mouse xenograft models from the early discovery stage. However, the BSA based dose conversion poorly predicts for the intravenous antibody and antibody drug conjugate anti-cancer drugs. For antibody-based drugs, five out of 30 (16.7%) predicted doses were within 3× of the recommended clinical dose. The body weight-based dose projection was modestly predictive with 66.7% of drugs predicted within 3× of the recommended clinical dose. The correlation was slightly better in ADCs (77.7% in 3×). The application and limitations of such simple dose estimation methods in the early discovery stage and in the design of clinical trials are also discussed in this retrospective analysis.https://www.frontiersin.org/articles/10.3389/fphar.2022.830972/fulloncologyeffective dosebody surface areapreclinical efficacytumor xenograft |
| spellingShingle | Robert J. Griffin Ethan Avery Cindy Q. Xia Predicting Approximate Clinically Effective Doses in Oncology Using Preclinical Efficacy and Body Surface Area Conversion: A Retrospective Analysis Frontiers in Pharmacology oncology effective dose body surface area preclinical efficacy tumor xenograft |
| title | Predicting Approximate Clinically Effective Doses in Oncology Using Preclinical Efficacy and Body Surface Area Conversion: A Retrospective Analysis |
| title_full | Predicting Approximate Clinically Effective Doses in Oncology Using Preclinical Efficacy and Body Surface Area Conversion: A Retrospective Analysis |
| title_fullStr | Predicting Approximate Clinically Effective Doses in Oncology Using Preclinical Efficacy and Body Surface Area Conversion: A Retrospective Analysis |
| title_full_unstemmed | Predicting Approximate Clinically Effective Doses in Oncology Using Preclinical Efficacy and Body Surface Area Conversion: A Retrospective Analysis |
| title_short | Predicting Approximate Clinically Effective Doses in Oncology Using Preclinical Efficacy and Body Surface Area Conversion: A Retrospective Analysis |
| title_sort | predicting approximate clinically effective doses in oncology using preclinical efficacy and body surface area conversion a retrospective analysis |
| topic | oncology effective dose body surface area preclinical efficacy tumor xenograft |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.830972/full |
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