Evaluation of the association between bevacizumab concentration and clinical outcomes in patients with breast cancer brain metastasis
Bevacizumab is widely used in various clinical indications, but investigations into its optimal dosage for treating CNS metastases remain limited. The BEEP regimen, comprising bevacizumab, etoposide, and cisplatin, has recently demonstrated promising clinical outcomes for patients with breast cancer...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402417421X |
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| author | Chih-Ning Cheng Yun-Jung Tsai Huai-Hsuan Chiu Tom Wei-Wu Chen Ching-Hung Lin Yen-Sheng Lu Ching-Hua Kuo |
| author_facet | Chih-Ning Cheng Yun-Jung Tsai Huai-Hsuan Chiu Tom Wei-Wu Chen Ching-Hung Lin Yen-Sheng Lu Ching-Hua Kuo |
| author_sort | Chih-Ning Cheng |
| collection | DOAJ |
| description | Bevacizumab is widely used in various clinical indications, but investigations into its optimal dosage for treating CNS metastases remain limited. The BEEP regimen, comprising bevacizumab, etoposide, and cisplatin, has recently demonstrated promising clinical outcomes for patients with breast cancer brain metastasis (BCBM) or leptomeningeal metastasis (LM). This study aimed to evaluate the exposure-response relationship of bevacizumab in BCBM patients and to explore the improved CNS penetration of chemotherapy by bevacizumab with LM patients. Twenty-two BCBM patients and six LM patients receiving the BEEP regimen were enrolled. For BCBM patients, blood samples were drawn at trough level of cycles 1 and 6 to investigate the association between bevacizumab concentrations and clinical outcomes. For LM patients, plasma and cerebrospinal fluid (CSF) concentrations of bevacizumab and etoposide were measured to investigate the enhancement of etoposide penetration provided by bevacizumab. Concentration evaluation revealed that bevacizumab plasma concentrations substantially varied between individuals. Additionally, concentrations increased after 6 cycles, indicating bevacizumab accumulation during treatment. Although bevacizumab concentrations did not associate with therapeutic response and progression-free survival, patients with higher bevacizumab concentrations exhibited longer overall survival (adjusted HR 0.78; p = 0.039). Furthermore, a positive correlation was observed between time-weighted average concentration of plasma bevacizumab and CSF penetration of etoposide on day 2 (post-bevacizumab) relative to day 1 (pre-bevacizumab) (r = 0.83; p = 0.042). These findings offer valuable insights into the application of therapeutic drug monitoring of bevacizumab to improve survival outcomes in BCBM patients. Further studies are warranted to determine the optimal bevacizumab concentration. |
| format | Article |
| id | doaj-art-67e6d1aa036b4a92b368941e2ceb4032 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-67e6d1aa036b4a92b368941e2ceb40322025-01-17T04:51:07ZengElsevierHeliyon2405-84402025-01-01111e41390Evaluation of the association between bevacizumab concentration and clinical outcomes in patients with breast cancer brain metastasisChih-Ning Cheng0Yun-Jung Tsai1Huai-Hsuan Chiu2Tom Wei-Wu Chen3Ching-Hung Lin4Yen-Sheng Lu5Ching-Hua Kuo6School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, TaiwanSchool of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, TaiwanDepartment of Medical Research, National Taiwan University Hospital, Taipei, TaiwanDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Oncology, National Taiwan University Cancer Center Hospital, Taipei, Taiwan; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Oncology, National Taiwan University Cancer Center Hospital, Taipei, TaiwanDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Oncology, National Taiwan University Cancer Center Hospital, Taipei, Taiwan; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan; Corresponding author. Department of Oncology, National Taiwan University Hospital, 7 Chung-Shan South Rd, Taipei 10002, Taiwan.School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; Corresponding author. School of Pharmacy, College of Medicine, National Taiwan University, Rm. 418, 4F., No.33, Linsen S. Rd., Chongsheng Dist., Taipei City, 100, Taiwan (ROC).Bevacizumab is widely used in various clinical indications, but investigations into its optimal dosage for treating CNS metastases remain limited. The BEEP regimen, comprising bevacizumab, etoposide, and cisplatin, has recently demonstrated promising clinical outcomes for patients with breast cancer brain metastasis (BCBM) or leptomeningeal metastasis (LM). This study aimed to evaluate the exposure-response relationship of bevacizumab in BCBM patients and to explore the improved CNS penetration of chemotherapy by bevacizumab with LM patients. Twenty-two BCBM patients and six LM patients receiving the BEEP regimen were enrolled. For BCBM patients, blood samples were drawn at trough level of cycles 1 and 6 to investigate the association between bevacizumab concentrations and clinical outcomes. For LM patients, plasma and cerebrospinal fluid (CSF) concentrations of bevacizumab and etoposide were measured to investigate the enhancement of etoposide penetration provided by bevacizumab. Concentration evaluation revealed that bevacizumab plasma concentrations substantially varied between individuals. Additionally, concentrations increased after 6 cycles, indicating bevacizumab accumulation during treatment. Although bevacizumab concentrations did not associate with therapeutic response and progression-free survival, patients with higher bevacizumab concentrations exhibited longer overall survival (adjusted HR 0.78; p = 0.039). Furthermore, a positive correlation was observed between time-weighted average concentration of plasma bevacizumab and CSF penetration of etoposide on day 2 (post-bevacizumab) relative to day 1 (pre-bevacizumab) (r = 0.83; p = 0.042). These findings offer valuable insights into the application of therapeutic drug monitoring of bevacizumab to improve survival outcomes in BCBM patients. Further studies are warranted to determine the optimal bevacizumab concentration.http://www.sciencedirect.com/science/article/pii/S240584402417421XBevacizumabTherapeutic drug monitoringOverall survivalLiquid chromatography–mass spectrometry |
| spellingShingle | Chih-Ning Cheng Yun-Jung Tsai Huai-Hsuan Chiu Tom Wei-Wu Chen Ching-Hung Lin Yen-Sheng Lu Ching-Hua Kuo Evaluation of the association between bevacizumab concentration and clinical outcomes in patients with breast cancer brain metastasis Heliyon Bevacizumab Therapeutic drug monitoring Overall survival Liquid chromatography–mass spectrometry |
| title | Evaluation of the association between bevacizumab concentration and clinical outcomes in patients with breast cancer brain metastasis |
| title_full | Evaluation of the association between bevacizumab concentration and clinical outcomes in patients with breast cancer brain metastasis |
| title_fullStr | Evaluation of the association between bevacizumab concentration and clinical outcomes in patients with breast cancer brain metastasis |
| title_full_unstemmed | Evaluation of the association between bevacizumab concentration and clinical outcomes in patients with breast cancer brain metastasis |
| title_short | Evaluation of the association between bevacizumab concentration and clinical outcomes in patients with breast cancer brain metastasis |
| title_sort | evaluation of the association between bevacizumab concentration and clinical outcomes in patients with breast cancer brain metastasis |
| topic | Bevacizumab Therapeutic drug monitoring Overall survival Liquid chromatography–mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S240584402417421X |
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