分子靶向药物在肝癌治疗中的地位.ppt

* * Bisphosphonates Overview * * Bisphosphonates Overview * * Phase II study of combining sorafenib with metronomic tegafur/uracil for advanced hepatocellular carcinoma Background & Aims: Sorafenib, a multi-kinase inhibitor with anti-angiogenic activity, was recently approved for the treatment of advanced hepatocellular carcinoma (HCC). Metronomic chemotherapy using tegafur/uracil (4:1 molar ratio), an oral fluoropyrimidine, has been shown to enhance the anti-tumor effect of anti-angiogenic agents in preclinical models. This phase II study evaluated the efficacy and safety of combining metronomic tegafur/uracil with sorafenib in patients with advanced HCC. Methods: Patients with histologically- or cytologically-proven HCC and Child-Pugh class A liver function were treated with sorafenib (400 mg twice daily) and tegafur/uracil (125 mg/m2 based on tegafur twice daily) continuously as first-line therapy for metastatic or locally advanced disease that could not be treated by loco-regional therapies. The primary endpoint was progression-free survival (PFS). Results: The study enrolled 53 patients. Thirty-eight patients (72%) were hepatitis B surface antigen-positive. The median PFS was 3.7 months (95% C.I., 1.9–5.5) and the median overall survival was 7.4 months (95% C.I., 3.4–11.4). According to RECIST criteria, 4 patients (8%) had a partial response and 26 patients (49%) had a stable disease. Major grade 3/4 toxicities included fatigue (15%), abnormal liver function (13%), elevated serum lipase (10%) hand-foot skin reaction (HFSR) (9%), and bleeding (8%). HFSR was the major adverse event resulting in dose reduction (19%) or treatment delay (21%). Conclusions: Metronomic chemotherapy with tegafur/uracil can be safely combined with sorafenib and shows preliminary activity to improve the efficacy of sorafenib in advanced HCC patients. * 文章尚未发表 Bisphosphonates Overview * * Purpose奥沙利铂 IV (85 mg/m2) 第1天 卡培他滨 (850 mg/m2 BID) 第1-7天 索拉非尼 (400 mg BID) 第1-14天（连续给药）