Phase 1/2 study of S-1 in combination with sorafenib for metastatic renal cell carcinoma
Mené sur 24 patients atteints d'un carcinome métastatique à cellules rénales, cet essai de phase I/II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité d'un traitement combinant S-1 et sorafénib
Background : The potential of S-1 for the treatment of metastatic renal cell carcinoma (mRCC) has been shown in two phase 2 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 1/2 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 1 primary endpoints 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 to 28 of a 42-day cycle in combination with sorafenib (400 or 800 mg/day), given daily with dose adjustment. In phase 2, the primary endpoint was to assess the overall response rate (ORR) at the RD. Results : Nine patients were enrolled into phase 1 and 21 (including 6 patients who received the RD in the phase 1 portion) were enrolled into phase 2. In the phase 1 portion, the MTD could not be determined, and the RD was defined as S-1 80 mg/m2/day on days 1–28+sorafenib 800 mg/day on days 1–42. In the phase 2 portion, 21 patients were fully assessable for efficacy and safety. The confirmed ORR was 52% (95% 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.