Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma:a prospective non.randomized study

Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.

使用mFOLFOX进行肝动脉灌注化疗与肝动脉化疗栓塞术治疗不可切除的巨块型肝细胞癌:一项前瞻性非随机研究

背景与目的肝动脉化疗栓塞术(transarterial chemoembolization,TACE)被推荐为巴塞罗那临床肝癌(Barcelona Clinic Liver Cancer,BCLC)A–B期的不可切除肝细胞癌(hepatocellular carcinoma,HCC)的标准治疗方法。然而,TACE对巨大(≥10 cm)A–B期HCC的疗效远不能令人满意,肝动脉灌注化疗(hepatic artery infusion chemotherapy,HAIC)被认为可能是该疾病更好的一线治疗方法。因此,我们比较了使用改良的FOLFOX方案(modified FOLFOX,mFOLFOX)进行HAIC与TACE治疗不可切除的巨块型HCC的安全性和有效性。方法一项前瞻性非随机II期研究在患有不可切除的巨块型HCC患者中开展。治疗方法为使用mFOLFOX方案每3周进行一次HAIC(奥沙利铂,85 mg/m^2动脉灌注;甲酰四氢叶酸,400 mg/m^2动脉灌注;氟尿嘧啶,400 mg/m^2静脉推注和2400 mg/m^2持续静脉滴注),使用50 mg表柔比星、50 mg洛铂、6 mg丝裂霉素和碘油聚乙烯醇颗粒进行TACE。评估了肿瘤反应、肿瘤进展时间(time-to-progression,TTP)和安全性。结果本研究共招募了79例患者:HAIC组38例,TACE组41例。HAIC组的部分缓解率和疾病控制率均高于TACE组(52.6%vs.9.8%,P<0.001;83.8%vs.52.5%,P=0.004)。HAIC和TACE组的中位TTP分别为5.87和3.6个月[风险比(hazard ratio,HR)=2.35,95%置信区间(confidence interval,CI)=1.16–4.76,P=0.015)]。HAIC组比TACE组有更多的患者接受了手术切除(10 vs.3,P=0.033)。HAIC组中3–4级不良事件(adverse events,AE)和严重不良事件(serious adverse events,SAE)发生数均低于TACE组(3–4级AE:13 vs.27,P=0.007;SAE:6 vs.15,P=0.044)。因无法耐受的治疗相关不良事件或撤回知情同意书而导致治疗提前终止的患者在TACE组中多于HAIC组(10 vs.2,P=0.026)。结论与TACE相比,使用mFOLFOX进行HAIC表现出显著优势的治疗反应性和更低的毒性。对于不可切除的巨块型HCC,HAIC可能是一种可行且有前景的一线治疗方法。