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Updated: Apr 8, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Phase I/II study of S-1 in combination with sorafenib for metastatic renal cell carcinoma
Background:
The potential of S-1 for the treatment of metastatic renal cell carcinoma (mRCC) has been shown in two phase II studies. We aimed to assess the safety, tolerance, pharmacokinetics and clinical activity of S-1 combined with sorafenib in patients with mRCC.
Patients And Methods:
In this multicenter, single-arm, open-label, phase I/II study of S-1 plus sorafenib, we recruited patients with clear-cell or papillary renal cell carcinoma who had received a maximum of one prior cytokine-based regimen. The phase I primary end points were the maximum tolerated dose (MTD) and recommended dose (RD). S-1 was administered orally at 60, 80, 100 or 120 mg/day on days 1-28 of a 42-day cycle in combination with sorafenib (400 or 800 mg/day), given daily with dose adjustment. In phase II, the primary end point was to assess the overall response rate (ORR) at the RD.
Results:
Nine patients were enrolled into phase I and 21 (including 6 patients who received the RD in the phase I portion) were enrolled into phase II. In the phase I portion, the MTD could not be determined, and the RD was defined as S-1 80 mg/m(2)/day on days 1-28 + sorafenib 800 mg/day on days 1-42. In the phase II portion, 21 patients were fully assessable for efficacy and safety. The confirmed ORR was 52% [95% confidence interval (CI) 29.8-74.3], including one complete response (5%) and 10 partial responses (48%). The median progression-free survival was 9.9 (95% CI 6.5-17.1) months. The most frequently reported treatment-related adverse event for all grades was hand-foot skin reaction (100%). The major reasons for dose reduction were hand-foot skin reaction (38%) and rash (14%).
Conclusion:
Combination therapy with S-1 plus sorafenib is effective and tolerable for patients with mRCC. However, skin events management is important in S-1 plus sorafenib combination therapy.
Insights
This study shows that combining S-1 with sorafenib is an effective treatment for metastatic renal cell carcinoma (mRCC). Careful management of skin side effects is crucial for patients undergoing this combination therapy.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Metastatic renal cell carcinoma (mRCC) treatment options are limited.
- Previous studies indicated S-1's potential in mRCC.
- Sorafenib is a targeted therapy used in various cancers.
Purpose of the Study:
- To evaluate the safety, tolerability, pharmacokinetics, and clinical activity of S-1 combined with sorafenib in mRCC patients.
- To determine the recommended dose (RD) for this combination therapy.
Main Methods:
- A multicenter, single-arm, open-label, phase I/II study.
- Patients with mRCC received S-1 plus sorafenib.
- Phase I focused on dose escalation to find the maximum tolerated dose (MTD) and RD.
- Phase II assessed the overall response rate (ORR) at the RD.
Main Results:
- The recommended dose (RD) was S-1 80 mg/m²/day plus sorafenib 800 mg/day.
- The overall response rate (ORR) in phase II was 52% (95% CI 29.8-74.3), including one complete response.
- Median progression-free survival was 9.9 months.
- Hand-foot skin reaction (100%) was the most frequent adverse event.
Conclusions:
- Combination therapy with S-1 and sorafenib demonstrates efficacy and tolerability in mRCC patients.
- Management of skin-related adverse events is essential for successful treatment.
- This combination offers a potential therapeutic option for mRCC.
