含奥沙利铂化疗方案治疗对索拉非尼耐药的晚期原发性肝癌的临床观察

目的回顾性分析含奥沙利铂（OXA）化疗方案治疗对索拉非尼耐药的晚期原发性肝癌的有效性和安全性。方法 2008年3月至2013年3月16例晚期原发性肝癌患者经索拉非尼一线治疗失败后，接受OXA为主的联合化疗，包括FOLFOX 4方案（OXA 85mg／m2 静滴， d1；亚叶酸钙200mg／m2静滴，d1、d2；氟尿嘧啶400mg／m2 静推，d1、d2；氟尿嘧啶600mg／m2持续静滴，d1、d2， 2周为1周期，每3个周期评价疗效），或XELOX方案化疗（OXA 130mg／m2静滴，d1；卡培他滨1250mg／m2口服，2次／日，d1～d14，3周为1周期，2个周期评价疗效）。按照RECIST 1.1版标准评价疗效，按照NCI CTC 3.0标准观察毒副反应，动态监测血清甲胎蛋白（AFP）变化，合并慢性乙型肝炎患者密切监测HBV DNA变化。结果16例患者中，化疗后有13例可以评价疗效，获PR 2例，SD 6例，PD 5例；有效率为15.4％（2／13），疾病控制率为61.5％（8／13），中位疾病进展期为110 天，中位总生存期为225天，AFP下降者占38.5％（5／13），2例出现HBV DNA再激活，经抗病毒治疗后恢复正常。主要毒副作用为骨髓抑制，包括血小板、白细胞、中性粒细胞减少，经白介素-11、重组人粒细胞集落刺激因子等治疗恢复正常。恶心、呕吐、腹泻、肝功损害以及外周神经毒性等轻微，经相关处理后好转。结论 对于索拉非尼耐药的晚期原发性肝癌患者，FOLFOX 4或XELOX方案具有一定疗效，毒副反应可以耐受，值得进一步研究。

Clinical observation of oxaliplatin-based regimen for sorafenib-resistant advanced primary liver carcinoma

Objective To evaluate clinical efficacy and adverse events of oxaliplatin（ OXA）-based regimen for patients with sorafenib-resistant advanced primary liver carcinoma. Methods Patients with sorafenib-resistant advanced primary liver carcinoma were treated with FOLFOX 4 or XELOX regimens. FOLFOX regimen was given as follow： OXA 85mg/m2 iv, d1; calcium folinate 200mg/m2 iv, d1, d2;fluorouracil（5-FU）400mg/m2 bolus,d1,d2;5-FU 600mg/m2 civ, d1,d2. Two weeks was a cycle. XELOX regi-men was applied as follow：OXA 130mg/m2 iv, d1;capecitabine 1250mg/m2 twice daily with oral administration,d1-d14 . Three weeks was a cycle. Tumor evaluation for FOLFOX 4 regimen was performed every 3 cycles and XELOX regimen was every 2 cycles. The time to progression（TTP）and overall survival（OS）were observed. Toxicities were evaluated according to NCI CTC 3？0. Serumα-fetoprotein （AFP）level was also monitored according to the schedule. HBV DNA was monitored for patients with HBV. Results The efficacy of 13 patients could be evaluated. No one achieved CR, PR in 2 patients, SD in 6 patients and PD in 4 patients. The response rate and disease control rate were 15？4% and 61？5%, respectively. The median TTP was 110 days and the median OS was 225 days. AFP de-creased rate was 38？5%. Hepatitis B virus reactivation was observed in 2 patients, and decreased to normal while receiving anti-HBV therapy. The main adverse event is myelosuppression including leucopenia and thrombocytopenia. Other adverse events including nause-a, vomiting, liver injury, periphery and neurotoxicity were well-tolerated. Conclusion FOLFOX 4 or XELOX regimen for patients with sorafenib resistant advanced primary liver carcinoma is effective and well-tolerable and further study should be taken to observe.