^(131)Ⅰ-美妥昔单抗联合肝动脉栓塞化疗治疗原发性肝癌的临床评价

Clinical evaluation of ^(131)I-Metuximab combination with TACE in treatment of hepataocellular carcinoma

目的评估原发性肝癌(HCC)患者通过肝动脉注射131I-美妥昔单抗同时行肝动脉栓塞化疗(TACE)的安全性、毒性作用及疗效。方法 35例HCC患者,美妥昔单抗皮试阴性,局麻下Seldinger法用5F导管经股动脉插管至肝动脉,超选择入肝动脉肿瘤供血分支,注入131I-美妥昔单抗27.75 MBq(含5 mg美妥昔单抗)/kg,20 min后注入含化疗药物(奥沙利铂50 mg和丝裂霉素10 mg)的碘化油乳剂和明胶海绵。患者给药后5 min、0.5 h、2 h、4 h、24 h、48 h、72 h、120 h和168 h采集外周血,并每日收集24 h尿液共7 d,计算药物动力学参数、毒性反应并评估疗效。结果分布半衰期(T1/2α)为(17.63±4.52)h,消除半衰期(T1/2β)为(61.32±10.38)h,峰值浓度(Cmax)为(39.72±15.79)kBq/ml,峰值时间(5.2±1.1)h。术后1周及4周毒性反应分级及患者肝功能Child-Pugh分级与术前相比差异有统计学意义(P<0.05或P<0.01)。术后4周34.29%(12/35)的患者甲胎蛋白(AFP)下降。11.43%(4/35)患者部分缓解(PR),85.71%(28/35)患者疾病稳定(SD),8.57%(3/35)患者疾病进展(PD),疾病控制率(PR+SD)为91.43%。6个月和1年的生存率分别为74.29%(26/35)和54.29%(19/35)。TNM分期为Ⅲ期的患者平均生存期(12.65±1.08)月,Ⅳ期患者平均生存期(9.3±0.89)月,两者有统计学差异(P<0.05)。结论 131I-美妥昔单抗联合TACE治疗HCC对于HCC伴门静脉分支癌栓且肝功能Child-Pugh A级患者耐受性较好。美妥昔单抗联合TACE治疗HCC使用27.75 MBq/kg剂量的美妥昔单抗,患者的耐受性和安全性较高。

Objective To evaluate the safety, toxicity and efficacy of 131 I-labeled-Metuximab （licartin） combination with transcatheter arterial chemoembolization （TACE） for the treatment of hepatocellular carcinoma （HCC）. Methods Thirty-five patients with HCC were enrolled in this study. After metuximab skin test presented negative, the 5F catheter was inserted in hepatic artery under local anesthesia by seldinger technique and entered su- perselectively into the blood-supply branch of hepatic artery of tumor, and then the licartin [ 27.75 MBq （ containing 5mg Metuximab）/kg] was injected via hepatic artery. After 20 minutes, the iodized oil emulsion and gelatin sponge containing chemotherapeutics （oxaliplatin 50mg, mitomycin 10 mg） were injected. The peripheral blood was collected after 5 minutes,0.5h,2h ,4h ,24h ,48h ,72h, 120h and 168h, and the 24h urine was collected everyday for 7 days. The parameters of pharmacokinetics were calculated,and the toxicity and efficacy were assessed. Results The distribution half-life was（ 17.63 ±4.52） h;eliminate half-life was（61.32 ± 10.38） h;peak concentration （Cmax） was （ 39.72 ± 15.79） kBq/ml; peak time was （ 5.2 ± 1.1 ） h. There are statistical difference in toxic reaction classification and liver function Child-Pugh classification between pre-treatment and 1 week,4 weeks post-treatwent（ P 〈 0.05 or P 〈 0.01 ）. After four weeks, alpha-fetoprotein （AFP） declined in the 34.29% （ 12/35 ） of patients. Partial remission （PR） was seen in 11.43% （4/35） of patients;stable disease （SD） was seen in 85.71% （28/35） of patients;progression of disease （PD） was seen in 8.57% （3/35） of patients;disease control rate （PR plus SD） was 91.43 %. Survival rates in 6 months and 1 year were 74.29% （26/35） and 54.29% （ 19/35 ）, respectively. The average survival time in patients with TNM III and 1V stages were（ 12.65 ± 1.08） months and （9.3 ±0.89） months respectively, and there was significant difference in the survival time between TNM III and IV stages （ P 〈 0.05）. Conclusions The patients with HCC complicated with tumor thrombus of portal vein branch and Child-Pugh A scale liver function have a good tolerance to the treatment of lieartin combination with TACE, and the safe dosage of licartin is 27.75 MBq/kg for the treatment of licartin combination with TACE.