S-1 (Tegafur/Gimeracil/Oteracil) for Breast Cancer
Yes, S-1 can be used to treat metastatic breast cancer and has demonstrated meaningful clinical activity with a favorable safety profile, particularly in Asian populations, though it is not a first-line standard therapy in most Western guidelines. 1
Evidence for Use in Breast Cancer
Clinical Efficacy Data
S-1 demonstrated a 41.7% overall response rate (CR+PR) in a Japanese phase II trial of 108 patients with metastatic breast cancer, with a median survival time of 872 days and low gastrointestinal toxicity. 1
A single-center retrospective study showed a 30.4% objective response rate and 50.0% clinical benefit rate, with median time to treatment failure of 10.7 months in 46 patients with metastatic breast cancer. 2
S-1 was generally well tolerated with only 4 patients discontinuing treatment due to adverse events, suggesting it maintains satisfactory quality of life. 2
Optimal Patient Selection
Patients most likely to benefit from S-1 therapy include those with:
- Disease-free interval ≥2 years (independent predictor of effectiveness, p=0.035). 2
- No visceral metastasis or limited visceral disease (higher clinical benefit rate, p=0.032). 2
- HER2-negative status (significantly higher response rates, p=0.020 for ORR and p=0.045 for CBR). 2
- No prior capecitabine therapy (higher effectiveness, p=0.049 for ORR and p=0.006 for CBR). 2
- Use as third-line treatment or earlier (significantly better outcomes, p=0.022 for ORR and p=0.019 for CBR). 2
Site-Specific Activity
- S-1 showed high clinical benefit rates in local disease (46.2%), lymph nodes (40.7%), bone (42.9%), and lungs/pleura (44.8%), but lower activity in liver metastases (30.0%). 2
Current Guideline Context
Primary Role in Gastric Cancer
S-1 is established as standard adjuvant therapy for gastric cancer in Asian populations, where it demonstrated 80.1% vs 70.1% 3-year overall survival after D2 resection (HR 0.68). 3
S-1 combined with trastuzumab and cisplatin showed comparable antitumor activity in HER2-positive gastric cancer in the Japanese HERBIS-1 study. 3
Limited Mention in Breast Cancer Guidelines
S-1 is not specifically mentioned in major Western breast cancer treatment guidelines (ESMO, ASCO) as a standard option. 3
One noninferiority trial in breast cancer used tegafur-uracil (UFT, a related compound) compared to CMF, establishing a framework for oral fluoropyrimidine use, but this does not represent current standard practice. 3
Dosing and Administration
Standard dose is 80 mg/m²/day administered orally twice daily (after breakfast and supper) for 28 consecutive days followed by 14-day rest. 1, 4
Dose adjustments based on body surface area: BSA <1.25 m² = 80 mg/day; 1.25-1.5 m² = 100 mg/day; ≥1.5 m² = 120 mg/day. 4
Pharmacokinetics are similar to continuous IV infusion of 5-FU, with no drug accumulation during consecutive administration. 4
Safety Profile
Common Toxicities (≥Grade 3)
- Neutropenia: 9.1%
- Anorexia: 3.6%
- Fatigue: 2.7%
- Stomatitis: 1.8%
- Nausea/vomiting: 1.8%
- Diarrhea: 0.9%
- No treatment-related deaths were observed. 1
Age Considerations
- No difference in response rate or toxicity between patients <65 years and ≥65 years, making it suitable for elderly patients. 1
Clinical Context and Positioning
S-1 should be considered as a later-line option (typically third-line or beyond) for metastatic breast cancer, particularly when:
- Standard chemotherapy options have been exhausted
- Patient prefers oral therapy
- Patient has favorable prognostic factors (long DFI, HER2-negative, no liver metastases)
- Maintaining quality of life is a priority 2
Important Caveats
Most evidence comes from Asian populations, and efficacy in Western patients is less well-established. 3
S-1 is primarily used in Japan and other Asian countries where it has regulatory approval for breast cancer; availability may be limited elsewhere. 1
For hormone receptor-positive metastatic breast cancer, endocrine-based therapy remains the preferred first-line approach unless visceral crisis is present. 5
Cross-resistance with capecitabine may occur, as both are oral fluoropyrimidines, though the addition of DPD inhibition in S-1 may provide some benefit. 2