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目的:在初步观察的基础上,探讨以奥沙利铂(OXA)和亚叶酸钙/5-氟尿嘧啶(LV/5-FU)组成的FOLFOX 4方案进行系统化疗,治疗无法手术切除的国人晚期肝细胞癌(HCC)患者的有效性和安全性。方法:前瞻性、单臂、开放性、多中心的II期临床研究,采取Simon二阶段法。经病理组织学和/或细胞学检查确诊的局部晚期、无法手术或已有远处转移的HCC患者,给予FOLFOX 4方案进行全身化疗,即OXA 85 mg.m-2,静滴,d 1;LV 200 mg.m-2,静滴2 h,d 1,d 2;5-FU 400 mg.m-2,静推,继以600 mg.m-2,持续静脉滴注22 h,d 1,d 2;每2周重复;直至疾病进展或最多不超过6个周期。每2个周期(6周时间)按照RECIST标准(1.0版)评价客观疗效,观察至疾病进展时间(TTP)和生存期(OS),并动态监测血清甲胎蛋白(AFP)的变化。一般毒性,按照NCI-CTC 2.0版标准观察和判定;神经系统毒性,参照OXA专用神经病变分级标准评判。结果:4家肿瘤中心参加,共入组25例患者,其中22例可以评估疗效,结果获得完全缓解(CR)1例,部分缓解(PR)3例,稳定(SD)7例,进展11例,客观缓解率(CR+PR)为18.2%,疾病控制率(DCR=CR+PR+SD)为50.0%;中位TTP为2.0个月(95%可信区间:1.3～4.0个月),中位OS为12.4个月。AFP反应率为28%。常见的毒性反应为粒细胞减少和轻度的周围神经毒性。结论:以奥沙利铂为主的FOLFOX 4方案进行系统化疗,对于国人晚期肝细胞癌具有良好的客观疗效和一定的生存获益,不良反应较轻,患者易于耐受,值得进一步开展大规模、随机对照的Ⅲ期临床研究。
OBJECTIVE: To investigate the systemic chemotherapy of FOLFOX 4 regimen consisting of oxaliplatin (OXA) and leucovorin / 5-fluorouracil (LV / 5-FU) for the treatment of unresectable Chinese advanced liver Effectiveness and safety of patients with cell carcinoma (HCC). METHODS: A prospective, single arm, open, multicenter phase II clinical trial was performed using Simon’s second-stage method. Patients with HCC who were locally or laterally diagnosed with histopathology and / or cytology, who had no surgical or distant metastases, were given systemic FOLFOX 4 regimen, ie OXA 85 mg.m-2, iv, d 1; LV 200 mg.m-2, intravenous infusion for 2 h, d 1, d 2 and 5-FU 400 mg.m-2, intravenous infusion followed by 600 mg.m-2 for 22 h, d 1 , d 2; repeated every 2 weeks; until disease progression or up to 6 cycles. The objective efficacy was evaluated according to RECIST criteria (version 1.0) every 2 cycles (6 weeks), and the time to progression (TTP) and survival (OS) were observed. The changes of serum alpha-fetoprotein (AFP) were also dynamically monitored. General toxicity, according to NCI-CTC 2.0 version of the standard observation and determination; nervous system toxicity, with reference to OXA special neuropathy grading criteria. RESULTS: Twenty-five patients were enrolled in the study. Twenty-two patients were evaluated for efficacy. One patient achieved complete remission (CR), three received partial remission (PR), seven received stabilization (SD) and 11 patients achieved progression , Objective response rate (CR + PR) was 18.2%, disease control rate (DCR = CR + PR + SD) was 50.0%; median TTP was 2.0 months (95% confidence interval: 1.3-4.0 months) The median OS was 12.4 months. AFP response rate of 28%. Common toxic reactions are neutropenia and mild peripheral neurotoxicity. Conclusions: Systemic chemotherapy with oxaliplatin-based FOLFOX 4 regimen has good objective efficacy and certain survival benefit for Chinese patients with advanced hepatocellular carcinoma. The adverse reactions are mild and the patients are easily tolerated. It is worth further carrying out large-scale , Randomized controlled phase III clinical study.