经导管肝动脉化疗栓塞联合索拉非尼治疗中晚期肝细胞癌的临床观察

目的 观察经导管肝动脉化疗栓塞(TACE)联合索拉非尼治疗中晚期肝细胞癌的有效性和安全性.方法 40例已接受过TACE治疗的中晚期肝细胞癌患者口服索拉非尼单药治疗,400mg,2次/d,直至病情进展或出现不可耐受的毒性反应.按照实体瘤疗效评价标准(RECIST)评价疗效,按照美国国立癌症研究所常见毒性事件标准(NCI-CTCAE)评价不良反应.结果 40例中晚期肝细胞癌患者中,获得完全缓解1例,部分缓解7例,疾病稳定19例,疾病进展13例,疾病控制率为67.5%.全组患者的生存时间为1～18个月,1年生存率为54.0%.主要不良反应为手足皮肤反应,其次是腹泻和血小板计数降低.结论 TACE联合索拉非尼治疗中晚期肝细胞癌是有效和安全的.     

肝动脉化疗栓塞联合索拉非尼治疗肝细胞癌合并肺转移的临床观察

目的 评价肝动脉化疗栓塞(TACE)联合索拉非尼治疗肝细胞癌(HCC)合并肺转移的疗效和安伞性.方法 30例伴有肺转移的晚期HCC患者,于TACE治疗后3周复查,如无禁忌证即开始服用索拉非尼,400 mg/次,2次/d;不能耐受时减至200 mg/次,2次/d.每4周进行疗效评估.结果 肺部转移病灶缩小6例,病灶稳定8例;肝脏病灶稳定22例,进展8例,在服药期问行TACE1～3次.不良反应包括手足皮肤反应7例,疲乏无力18例,脱发6例,腹泻6例,贫血和骨髓抑制5例,高血压2例,消化道出血1例.结论 HCC合并肺转移时,TACE联合索拉非尼治疗可有效控制疾病进展,安伞性及患者耐受性良好.     

肝动脉化疗栓塞联合索拉非尼治疗肝细胞癌合并肺转移的临床观察

目的 评价肝动脉化疗栓塞(TACE)联合索拉非尼治疗肝细胞癌(HCC)合并肺转移的疗效和安伞性.方法 30例伴有肺转移的晚期HCC患者,于TACE治疗后3周复查,如无禁忌证即开始服用索拉非尼,400 mg/次,2次/d;不能耐受时减至200 mg/次,2次/d.每4周进行疗效评估.结果 肺部转移病灶缩小6例,病灶稳定8例;肝脏病灶稳定22例,进展8例,在服药期问行TACE1～3次.不良反应包括手足皮肤反应7例,疲乏无力18例,脱发6例,腹泻6例,贫血和骨髓抑制5例,高血压2例,消化道出血1例.结论 HCC合并肺转移时,TACE联合索拉非尼治疗可有效控制疾病进展,安伞性及患者耐受性良好.     

索拉非尼联合经导管肝动脉化疗栓塞治疗无远处转移的晚期肝细胞癌

目的　观察多靶点分子靶向治疗药物索拉非尼联合经导管肝动脉化疗栓塞（ＴＡＣＥ）治疗不伴远处转移的晚期或进展期肝细胞癌的疗效和不良反应。方法　２００７年４月至２００９年９月,中国医学科学院肿瘤医院收治４５例不伴有远处转移的晚期或进展期肝细胞癌患者,口服索拉非尼治疗,其中１８例联合ＴＡＣＥ（１～５次）,２７例单用索拉非尼。索拉非尼起始剂量４００ｍｇ,每日２次,治疗过程中根据不良反应发生情况调整用量。每２个月评价疗效和不良反应,并随访中位至疾病进展时间（ＴＴＰ）和中位总生存时间（ＯＳ）。结果　至２００９年１２月,４０例患者达到临床评价要求（联合ＴＡＣＥ１８例,单用索拉非尼２２例）。两组不良反应发生率无显著差异,主要治疗相关不良反应为手足皮肤反应、腹泻和高血压。两组患者均无４级严重不良反应。索拉非尼联合ＴＡＣＥ组中位ＴＴＰ为１０.０个月,中位ＯＳ１６.０个月;单用索拉非尼组中位ＴＴＰ为４.５个月,中位ＯＳ５.３个月。两组ＯＳ和ＴＴＰ差异有统计学意义（Ｐ＜０.０１）。结论　病变局限在肝内且不合并远处转移的晚期或进展期肝细胞癌患者,口服索拉非尼联合ＴＡＣＥ不增加并发症发生率,且生存预后改善。     

经导管肝动脉化疗栓塞联合索拉非尼治疗不能手术切除肝细胞肝癌的疗效

目的探讨经导管肝动脉化疗栓塞联合索拉非尼对不能手术切除的中晚期肝细胞肝癌的疗效。方法选取收治的肝细胞肝癌患者160例,采用随机数字法分为联合组(n=82)和对照组(n=78)。联合组患者给予经导管肝动脉化疗栓塞联合索拉非尼治疗,对照组患者给予经导管肝动脉化疗栓塞治疗。比较两组患者治疗后疗效、生活质量、肝功能状况、生存率和不良反应情况。结果联合组患者治疗总有效率和生活质量改善率分别为97.6%(80/82)和89.0%(73/82),优于对照组的59.0%(46/78)和53.9%(42/78,P<0.0.5);两组患者治疗后丙氨酸氨基转移酶(ALT)和总胆红素(TBIL)水平均高于治疗前(均P<0.05),而治疗前后白蛋白(ALB)水平差异无统计学意义(P>0.05);联合组患者1、2年生存率均高于对照组(均P<0.05);两组患者不良反应发生率差异无统计学意义(P=0.557)。结论经导管肝动脉化疗栓塞联合索拉非尼治疗疗效优于单经导管肝动脉化疗栓塞治疗,可有效改善患者的生活质量和肝功能,提高生存率。     

索拉非尼联合经导管动脉栓塞化疗治疗不可手术切除的原发性肝癌患者的临床疗效及安全性

目的 探讨索拉非尼联合经导管动脉栓塞化疗（TACE）治疗不可手术切除的原发性肝癌患者的临床疗效及安全性。方法 选取120例不可切除原发性肝癌患者,依据治疗方法分为联合组（n=55）和对照组（n=65）,其中对照组患者给予单纯TACE治疗,联合组患者给予索拉非尼联合TACE治疗。比较两组患者的近期疗效、血清肿瘤标志物[甲胎蛋白（AFP）]水平、肝功能指标[谷草转氨酶（AST）、谷丙转氨酶（ALT）、白蛋白（ALB）]水平、不良反应发生情况及远期生存情况。结果 联合组患者的疾病控制率（DCR）为74.55%,高于对照组患者的56.82%(P﹤0.05)。治疗12周,两组患者血清AFP水平均低于本组治疗前,且联合组患者血清AFP水平低于对照组（P﹤0.05）。治疗前及治疗12周,两组患者血清AST、ALT、ALB水平组间及组内比较,差异均无统计学意义（P﹥0.05）。联合组患者腹痛腹泻、皮疹、手足皮肤反应发生率均明显高于对照组（P﹤0.01）。联合组患者中位总生存期为14个月,长于对照组患者的10个月（P﹤0.05）,1、2年总生存率分别为74.55%、45.45%,均高于对照组患者的55....     

经导管肝动脉栓塞治疗肝癌的远期疗效观察

262例原发性肝癌行经导管肝动脉注射碘油抗癌药混悬剂栓塞化疗（LP－TAE）后随访4～5年，生存3年以上52例，其中27例生存4年以上，8例生存5年以上，3、4、5年累计生存率分别为21．04％，11．64％和4．03％（寿命表法）。与同期生存3年以内的210例对照比较，结果表明病程分期、肝功能、肿瘤大小与生长方式、肿瘤供血丰富程度、是否伴有门脉癌柱与A－V分流、是否加用明胶海绵栓塞、Lp－TAE后碘油沉积范围、治疗后肿瘤缩小程度、AFP是否降为正常、是否伴发肝内外转移是影响肝癌Lp－TAE远期疗效的重要因素。     

ＴＡＣＥ联合索拉非尼治疗肝细胞癌的临床观察

目的　探讨ＴＡＣＥ联合索拉非尼治疗肝细胞癌的疗效及安全性。方法　回顾性分析我院口服索拉非尼３个月以上,并行ＴＡＣＥ的１３例肝细胞癌患者,计算其生存率、治疗间隔、毒副反应及疾病进展时间。结果　全组平均存活时间３６.６个月,３例患者达到ＰＲ,４例ＳＤ,６例ＰＤ,临床受益率为５４％。口服索拉非尼前,平均ＴＡＣＥ间隔时间为６7天;口服索拉非尼后,平均间隔１０３天。全组３级高血压及手足皮肤反应各３例,余７例患者未发生其他３级以上毒副反应。全组平均疾病进展时间为２１０天。发生３级毒副反应的患者平均疾病进展时间为３１３天,未发生３级以上毒副反应的患者平均疾病进展时间为１２２天（Ｐ＝０.０５３）。结论　ＴＡＣＥ与索拉非尼联合治疗晚期肝细胞癌是安全、有效的。     

索拉非尼治疗晚期肝细胞癌１０例临床观察

目的　观察索拉非尼治疗国人晚期肝癌的临床疗效及不良反应。方法　１０例晚期肝细胞癌患者口服索拉非尼４００ｍｇ,每日２次,至少用药６周以上评价疗效。结果　１０例患者均可评价疗效,获得ＣＲ０例,ＰＲ２例,ＳＤ３例,ＰＤ５例,中位ＴＴＰ为４.５个月。主要不良反应为皮疹、腹泻、恶心、呕吐以及手足皮肤反应。结论　索拉非尼治疗国人晚期肝癌患者的疗效较好,不良反应可以耐受。     

索拉非尼治疗晚期肝细胞癌３６例临床观察

目的　观察索拉非尼治疗晚期肝细胞癌的疗效及毒副作用。方法　３６例晚期肝癌患者口服索拉非尼４００ｍｇ,每天２次,按照ＲＥＣＩＳＴ标准评价客观有效率（ＯＲＲ）、疾病控制率（ＤＣＲ）以及中位肿瘤进展时间（ｍＴＴＰ）、中位生存时间（ｍＯＳ）。结果　全组获ＰＲ４例（１１.１１％）,ＭＲ６例（１６.６６％）,ＳＤ１２例（３３.３3％）,ＰＤ１４例（３８.８８％）,ＯＲＲ为１１.１１％,ＤＣＲ６１.１％。出现手足皮肤反应２２例（６１.１１％）,腹泻６例（１６.６６％）,高血压２例（５.５５％）,骨髓抑制４例（１１.１１％）。生存３个月３４例（９４.４４％）,６个月２９例（８０.5５％）,９个月２５例（６９.４４％）,１年以上２例,ｍＯＳ为１０.９个月,ｍＴＴＰ５.２个月。生存质量改善１８例（５０％）,稳定１０例（２７.７７）,降低为８例（２２.２２％）。结论　索拉非尼治疗晚期肝癌疗效好,毒副反应较轻。     

The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: Final results of the START trial

This phase II, investigator‐initiated, prospective single‐arm multinational study ( ClinicalTrials.gov registration NCT00990860) evaluated sorafenib in combination with doxorubicin‐based transarterial chemoembolization (TACE) in patients with intermediate‐stage, unresectable hepatocellular carcinoma (HCC). Patients with histologically or clinically diagnosed HCC received TACE with interrupted dosing of sorafenib (sorafenib discontinued for 3 days before and 4–7 days after TACE). TACE/sorafenib cycles were repeated every 6–8 weeks. Primary and secondary objectives were, respectively: to evaluate the safety and tolerability of TACE combined with sorafenib, and also their efficacy. The full analysis set comprised 192 patients (mean age 56.1 years). Most were male (87.0%), Eastern Cooperative Oncology Group (ECOG) score 0 (81.8%), Child‐Pugh A (91.8%) and Barcelona Clinic Liver Cancer (BCLC) stage B (81.5%); 81.2% had chronic hepatitis B. Combined TACE/sorafenib was well tolerated, with only 8.1% of patients discontinuing owing to adverse events (AEs). The most common grade ≥3 AEs were palmar‐plantar erythrodysesthesia syndrome (15.1%) and decreased platelet count (10.9%). Serious AEs (SAEs) occurred in 52 patients during the study; however, only four were considered related to sorafenib. A mean of 2.7 TACE cycles were administered and 52.6% of patients achieved complete response in target lesions; 16.8% achieved partial response, and 5.8% had progression of disease as their best response, evaluated by modified RECIST. Median progression‐free survival and time to progression were 384 and 415 days, respectively, and the estimated 3‐year overall survival was 86.1%. This study suggests that the combination of TACE and sorafenib is well tolerated and efficacious; the interrupted sorafenib dosing schedule may have contributed to a considerably lower AE profile than observed in other combination trials.     

肝动脉化疗栓塞术联合射频消融术治疗小肝癌的研究进展

原发性肝癌是世界性常见的恶性肿瘤之一,肝癌的早发现早治疗已成为临床研究的重点。射频消融术(RFA)在国内外已成为公认的对小肝癌治疗有效的一种手段,尤其对于直径小于3cm的小肝癌患者,治愈率已经达到甚至超过外科切除治疗。在治疗直径大于3cm的小肝癌患者,单一的RFA治疗复发率相对较高。肝动脉化疗栓塞(TACE)对小肝癌的治疗效果早已获得承认,但也存在一定的缺点。TACE术后改变了原有的动脉供血系统,侧支循环容易建立,病灶坏死率较低,复发率较高,多次TACE治疗会加重肝功能的损害。TACE与RAF联合能在小肝癌患者治疗中取长补短,提高治疗的安全性、有效性,以及对患者的远期疗效。本文主要对肝动脉化疗栓塞术联合射频消融术治疗小肝癌的现状及其进展做一综述。     

Interim analysis of START: Study in asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial

Transarterial chemoembolization (TACE) represents a first‐line noncurative therapy for hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown to be effective and safe monotherapy in patients with advanced HCC and the current study reports the interim results of a prospective Phase II, open label, trial investigating the safety and efficacy of the combination of sorafenib and conventional TACE in patients from the Asia‐Pacific region with intermediate HCC. Patients with histologically or clinically diagnosed HCC were treated with conventional TACE followed by sorafenib 4 to 7 days later. TACE was performed by selective transarterial chemotherapy in the vessels feeding the tumor with an emulsion of lipiodol (5–20 ml) and doxorubicin (30–60 mg) followed by embolization with absorbable particles (gel foam). TACE/sorafenib cycles were repeated every 6–8 weeks. Primary objectives were to evaluate the safety and tolerability, in addition to the efficacy of TACE combined with sorafenib for HCC. A total of 147 patients were included in the intention‐to‐treat analysis and received at least one dose of sorafenib. Gastrointestinal AEs were reported by 62.6% of patients while 57.8% reported skin AEs although most were mild to moderate. The mean number of cycles undertaken was 2.1 and 63.3% of patients achieved either partial response or stable disease. Clinically, the disease control rate was 91.2% while the overall response rate was calculated as 52.4%. Our study shows that concurrent sorafenib and TACE therapy is safe and effective with no unexpected side effects.     

Radiotherapy combined with transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma - a prospective clinical trial

Objective： This study evaluated the therapeutic effect of external beam radiotherapy （RT） combined with transcatheter arterial chemoembolization （TACE） on the patients with unresectable hepatocellular carcinoma （HCC）. Methods： From June 1994 to April 2002, 114 patients with unresectable HCC were nonrandomized prospectively stepped into our study. All patients received TACE as initial therapy, except 54 also received combination therapy with external beam therapy. Survival failure patterns were analyzed and compared between the two groups. Results： Overall survival rates in the patients in the radiotherapy group were 65%, 47%, 38% at 1,2, 3 years, respectively, improved over the non-radiotherapy group rates of 54%, 36.5%, 18% at 1, 2, 3 years, respectively. There was significant difference between two groups （P 〈 0.05）. The survival rates correlated with tumor size, number of tumors, and portal vein embolus. Conclusion： TACE combined with RT is a more effective treatment than TACE alone in patients with unresectable HCC.     

Advanced hepatocellular carcinoma treated by transcatheter arterial chemoembolization with drug-eluting beads plus lenvatinib versus sorafenib,a propensity score matching retrospective study

Recently, a prospective randomized study suggested that transcatheter arterial chemoembolization (TACE) plus lenvatinib, as opposed to TACE plus sorafenib, was an effective and promising treatment for patients with advanced hepatocellular carcinoma (HCC) having portal vein thrombus (PVTT) and large tumor burden. However, no propensity score matching retrospective studies on TACE with drug-eluting beads (DEB-TACE) plus lenvatinib (DEB-TACE+LEN) versus DEB-TACE plus sorafenib (DEB-TACE+SOR) for advanced HCC has been reported to date. The medical records of consecutive patients with advanced HCC who underwent DEB-TACE+LEN or DEB-TACE+SOR between January 2017 and December 2020 were retrospectively reviewed. Mutation genes (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by whole-exome sequencing (WES). Adverse events (AEs), objective response rate (ORR), disease control rate (DCR), overall survival (OS) and time to progression (TTP) were compared between patients who underwent DEB-TACE+LEN and DEB-TACE+SOR. In total, 150 patients were enrolled in this study. The DEB-TACE+LEN group (n=50) showed significantly better ORR (64.0% vs. 33.3%; P=0.008), OS (hazard ratio [HR]=0.63, 95% confidence interval (CI): 0.41-0.98; P=0.043), and TTP (HR=0.65, 95% CI: 0.45-0.94; P=0.023) than that in the DEB-TACE+SOR group (n=100). Subgroup analyses showed that in patients with portal vein tumor thrombus (PVTT), OS and TTP were significantly longer in the DEB-TACE+LEN group than in the DEB-TACE+SOR group (HR=0.59, 95% CI: 0.36-0.98; P=0.043; HR=0.89, 95% CI: 0.35-2.29; P=0.035). In patients with FGF21 amplification, OS was also significantly longer in the DEB-TACE+LEN group than that in the DEB-TACE+SOR group (HR=0.19, 95% CI: 0.06-0.66; P=0.003). The patients in DEB-TACE+LEN group had a significantly lower incidence of hand-foot skin reaction (32.0% vs. 49.0%; P=0.048), but a higher incidence of proteinuria (26.0% vs. 10.0%; P=0.010) than that in the DEB-TACE+SOR group. In conclusion, DEB-TACE+LEN conferred better ORR, OS and TTP than did DEB-TACE+SOR in patients with advanced HCC, especially those with PVTT and FGF21 amplification, with acceptable AEs; thus making it a superior treatment modality for these patients.     

Exploring the efficacy and safety of single-agent sorafenib in a cohort of Italian patients with hepatocellular carcinoma

This study investigates the effectiveness and safety of sorafenib in a heterogeneous cohort of Child–Pugh A, B and C patients with advanced hepatocellular carcinoma in a clinical-practice scenario. Adult patients with hepatocellular carcinoma and treated with sorafenib 800 mg/day were eligible for this multicentric retrospective observational study. Safety analyses were performed and the effectiveness of sorafenib was assessed in terms of time to progression (TTP) and overall survival (OS). In total, 93 patients were enrolled: 14 were Child–Pugh A, 70 were Child–Pugh B and nine were Child–Pugh C. No differences in the frequency of grade 3 adverse events among different Child–Pugh classes were reported. In the overall cohort, median OS was 12 months (95% CI: 11.7–12.8 months) and TTP was 3 months (95% CI: 2.5–3.4 months). The Child–Pugh score had a statistically significant effect on TTP: 6.6 months in Child–Pugh A, 2.8 months in Child–Pugh B and 2.0 months in Child–Pugh C patients (p = 0.012). To our knowledge, this study includes the largest cohort of Caucasian Child–Pugh B and C patients ever treated with sorafenib. Although the retrospective design of this study does not allow reaching any definite conclusion, the results could lend some preliminary support to the safety and the effectiveness of sorafenib monotherapy in patients with Child–Pugh B and Child–Pugh C liver function.     

肝动脉化疗栓塞术后胸腺法新联合索拉菲尼治疗中晚期肝癌的疗效分析

目的:探讨中晚期肝细胞型肝癌患者肝动脉化疗栓塞术(transcatheter arterial chemoembolization,TACE)后索拉菲尼联合胸腺法新的疗效分析.方法:回顾性研究第四军医大学附属唐都医院54例中晚期原发性肝癌患者,所有患者均为乙型肝炎表面抗原阳性,并均接受了TACE手术治疗.在手术治疗后三天,开始口服索拉菲尼,以及皮下注射胸腺法新,观察患者的肝功能,计算治疗的有效率以及患者的生存时间.结果:观察组患者的总体有效率82.8%,显著高于对照组的56%,差异有统计学意义(P=0.032);观察组平均生存时间为13.8个月,对照组为10.2个月,可认为观察组生存时间长于对照组(P=0.021);治疗前两组AST、ALT以及白蛋白无明显差异(P>0.05);治疗3个月后与治疗前相比,两组的AST和ALT均得到改善(P<0.05),并且观察组白蛋白提高(P<0.001).结论:胸腺法新、索拉菲尼联合TACE的治疗方法可以有效的改善肝炎病毒所致的原发性肝癌的预后,提高患者的生存期,值得临床推广.     

Phase I study of combination chemotherapy using sorafenib and transcatheter arterial infusion with cisplatin for advanced hepatocellular carcinoma

The aims of this study were to evaluate the frequency of dose‐limiting toxicities and to find the recommended dose of combination chemotherapy with sorafenib and transcatheter arterial infusion (TAI) using cisplatin for patients with advanced hepatocellular carcinoma (HCC), for whom surgical resection, local ablation therapy, or transcatheter arterial chemoembolization were not indicated. Patients received 800 mg sorafenib daily. Cisplatin was given at one of three dosages (level 1, 35 mg/m²/cycle; level 2, 50 mg/m²/cycle; and level 3, 65 mg/m²/cycle) from feeding arteries to the HCC. The treatment was repeated every 4–6 weeks up to a maximum of six cycles, until there were signs of tumor progression or unacceptable toxicity. The dose‐limiting toxicities experienced by the 20 enrolled patients were grade 4 increased aspartate aminotransferase at level 1, grade 3 gastrointestinal hemorrhaging at level 1, and grade 3 hypertension at level 3. The common drug‐related adverse events that were of severity grade 3 or 4 included the elevation of aspartate aminotransferase (30%), alanine aminotransferase (20%), amylase (30%), and lipase (30%). Partial response was seen in four patients (20%), and 13 patients (65%) had stable disease. The median overall survival and progression‐free survival were 9.1 and 3.3 months, respectively. The combination of sorafenib at 800 mg/day with TAI of cisplatin at 65 mg/m²/cycle was determined to be the recommended regimen. A randomized phase II trial of sorafenib alone versus sorafenib plus TAI of cisplatin is currently underway. This study was registered at UMIN as trial number UMIN000001496.     

肝动脉栓塞化疗结合无水酒精注射治疗中晚期原发性肝癌疗效分析

Objective:To evaluate the clinical efficacy of the combined treatment with transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) on hepatocellular carcinoma (HCC). Methods:312 patients with moderate or advanced HCCs were divided into two groups: 170 cases underwent TACE treatment alone, 142 cases were treated with TACE and PEI under B-ultrasotmd guidance. Results:The rates of reduction in tumor diameter and the decline in serum AFP level were 41.2% and 40.4% in the TACE group and 75.4% and 74.1% in the TACE PEI group respectively. The 6, 12 and 24 months survival rates in the TACE group were 77.1%,34.1% and 18.8%,respectively and in the TACE PEI group 87.3%, 62.0% and 38.0%, respectively. Overall, there was a significant difference between the two treatment groups (P＜0.05). Conclusion：Treatment on HCCs with TACE PEI is convenient, safe and results in better survival rates than TACE alone.