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Orally administered S-1 suppresses circulating endothelial cell counts in metastatic breast cancer patients
Wakako Tsuji1, Hiroshi Ishiguro, Sunao Tanaka
1Division of Breast Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto, Japan, w-sato@kuhp.kyoto-u.ac.jp.
Background:
S-1 is an oral cytotoxic preparation that contains tegafur. Gamma-butyrolactone (GBL) is a metabolite of tegafur that is known to suppress vascular endothelial growth factor (VEGF)-mediated angiogenic activity. The aim of this study was to determine the change in circulating endothelial cell (CEC) counts, GBL levels, and angiogenesis-related factors during S-1 administration in metastatic breast cancer (MBC) patients.
Methods:
Patients with HER2-negative MBC were eligible. S-1 was administered orally twice daily in a 4 week on/2 week off cycle until disease progression or unacceptable toxicity occurred. Blood was collected on the following: days 1, 43, 85 (before each cycle of S-1 administration), days 15, 57 (1 h after S-1 administration), and day 29. The CellSearch(®) system was used to count the CECs. The gas chromatographic-mass spectrometric method was used to measure plasma GBL and 5-FU levels. Levels of VEGF were assayed by enzyme-linked immunosorbent assay.
Results:
A total of 18 patients were enrolled. The plasma GBL levels on days 15 and 57 were 41.3 ± 15.8 and 41.0 ± 11.2 ng/mL, respectively. The CEC levels decreased on day 15, and significantly low levels were maintained until day 85 (P = 0.002 vs day 1). The plasma VEGF levels significantly decreased on day 15 (P = 0.012 vs day 1) and had a tendency to decrease until day 57.
Conclusions:
This exploratory study showed that GBL levels increased, VEGF levels decreased, and CEC levels were suppressed during S-1 administration. S-1 appears to have anti-angiogenic activity.
Insights
S-1 treatment in metastatic breast cancer patients increased gamma-butyrolactone (GBL) levels and suppressed circulating endothelial cell (CEC) counts and vascular endothelial growth factor (VEGF) levels, indicating anti-angiogenic activity.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- S-1, an oral cytotoxic drug containing tegafur, is used for cancer treatment.
- Gamma-butyrolactone (GBL), a tegafur metabolite, inhibits vascular endothelial growth factor (VEGF)-mediated angiogenesis.
- Metastatic breast cancer (MBC) poses significant treatment challenges, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the anti-angiogenic effects of S-1 in HER2-negative MBC patients.
- To assess changes in circulating endothelial cell (CEC) counts during S-1 therapy.
- To monitor plasma levels of GBL and VEGF in response to S-1 administration.
Main Methods:
- HER2-negative MBC patients received S-1 orally in a 4-week on/2-week off cycle.
- Blood samples were collected at multiple time points during S-1 treatment.
- Circulating endothelial cell (CEC) counts were determined using the CellSearch® system.
- Plasma GBL, 5-FU, and VEGF levels were measured using gas chromatography-mass spectrometry and ELISA.
Main Results:
- Plasma GBL levels increased during S-1 administration.
- CEC levels significantly decreased from day 1 to day 85 (P = 0.002).
- Plasma VEGF levels significantly decreased on day 15 (P = 0.012) and showed a decreasing trend until day 57.
Conclusions:
- S-1 administration leads to increased GBL levels and suppressed CEC and VEGF levels in MBC patients.
- These findings suggest that S-1 exhibits anti-angiogenic activity.
- S-1 holds potential as a therapeutic agent for managing angiogenesis in metastatic breast cancer.
