以索拉非尼为基础治疗晚期肝细胞癌的疗效和不良反应临床观察

Clinical observation on efficacy and adverse reactions of sorafenib in treating advanced hepatocellular carcinoma

背景与目的:多激酶抑制剂索拉非尼因SHARP(Sorafenib HCC Assessment RandomizedProtocol)和ORIENTAL(Sorafenib in Patients in Asia-pacific Region with Hepatocellular Carcinoma)2项Ⅲ期临床试验证实能显著改善无进展生存期(progress free survival,PFS)和延长疾病进展时间(time toprogression,TTP)和总生存期(overall survival,OS),2008年被批准为晚期肝细胞癌的治疗。本研究观察索拉非尼单用或联合TACE治疗30例晚期肝细胞癌的疗效和不良反应。方法:选择2009年3月—2011年1月,符合晚期原发性肝癌临床或病理诊断的患者30例,每次口服索拉非尼400 mg,每日2次,至少口服2个月以上,其中20例联合1～9次TACE,10例单用索拉非尼治疗。按RESIST标准,每2个月评价疗效,随访TTP和OS。结果:30例患者部分缓解(PR)3例,疾病稳定(SD)16例,疾病进展(PD)11例,临床获益率(clinical benefit rate,CBR)为63.3%。其中10例单用索拉非尼组PR 1例,SD 5例,PD 4例,CBR为60.0%;20例联合治疗组PR 2例,SD 11例,PD 7例,CBR为65.0%。27例患者生存3个月,24例6个月,21例9个月,9例1年以上,全组TTP为7个月,OS为9个月。联合组患者TTP为7个月,OS为14个月,单用索拉非尼组患者TTP为6个月,OS为9个月,差异无统计学意义(P>0.05)。患者用药1～2周开始出现不良反应,手足皮肤反应23例,腹泻24例,高血压14例,乏力24例,脱发9例,出现3度不良反应10例,给予对症治疗后,均能完成治疗。结论:索拉非尼联合TACE治疗较单用索拉非尼治疗可延长患者的TTP和OS,但两组差异无统计学意义(P>0.05)。两组患者不良反应可耐受,不良反应发生率差异无统计学意义(P>0.05)。

Background and purpose：Two clinical trials SHARP and ORIENTAL confirmed that sorafenib,a multi-kinase inhibitor could significantly improve PFS as well as TTP,and prolong OS for patients with hepatocellular carcinoma.Therefore sorafenib was approved to treat advanced hepatocellular carcinoma in 2008.Our study was designed to observe efficacy and adverse reactions of sorafenib alone or in combination with TACE in treating 30 patients with advanced hepatocellular carcinoma.Methods：From Mar 2009 to Jan 2011,a total of 30 patients with clinical or pathological diagnosis of advanced primary hepatocellular carcinoma orally took sorafenib with dosage of 400 mg each time,2 times a day,and treatment duration was at least more than 2 months.Twenty patients received TACE for 1 to 9 times in combination with sorafenib,and 10 patients took sorafenib alone.In accordance with RESIST,efficacy was evaluated each two-month and follow-up was performed to achieve TTP and OS.Results：Among 30 patients,there were 3 patients of PR,16 patients of SD,and 11 patients of PD,with clinical benefit rate（CBR） of 63.3%.Among 10 patients who took sorafenib alone,there were 1 patient of PR,5 patients of SD,and 4 patients of PD,with CBR of 60.0%.Among 20 patients who took sorafenib in combination with TACE,there were 2 patients of PR,11 patients of SD,and 7 patients of PD,with CBR of 65.0%.All 27 patients survived for more than 3 months,24 patients survived for more than 6 months,21 patients survived for more than 9 months,and 9 patients survived for even more than 1 year.TTP was 7 months,and OS was 9 months,with P=0.067 2 and P=0.058 9.Patients demonstrated adverse effects 1-2 weeks after administration.Twenty-three patients had hand and foot symptom,24 patients had diarrhea,14 patients had hypertension,24 patients had fatigue,9 patients had hair loss.There were 10 cases of degree 3 adverse reaction in total,and patients could accomplish the whole therapy after receiving symptomatic treatments.There were no significant differences between two groups in adverse reactions.Conclusion：Sorafenib in combination with TACE may prolong TTP and OS for patients with advanced hepatocellular carcinoma comparing to sorafenib alone,however,there were no significant differences.Adverse reactions of two groups were both tolerable and there were no significant differences.