目的 觀察注射用卡瑞利珠單抗聯(lián)合鹽酸安羅替尼膠囊和FOLFOX方案（奧沙利鉑、亞葉酸鈣和氟尿嘧啶）治療晚期肝癌的臨床療效。方法 選取2018年1月—2019年12月海南醫(yī)學(xué)院第二附屬醫(yī)院、海南醫(yī)學(xué)院第一附屬醫(yī)院收治的126例晚期肝癌患者作為研究對象，根據(jù)治療方式不同分為對照組和治療組，每組各63例。兩組均給予FOLFOX方案：第1天靜脈滴注注射用奧沙利鉑，85 mg/m²加5%葡萄糖注射液250 mL，靜脈滴注2 h；第1、2天靜脈滴注注射用亞葉酸鈣，200 mg/m²加5%葡萄糖注射液250 mL，靜脈滴注2 h；第1、2天靜脈推注氟尿嘧啶注射液，400 mg/m²，同時持續(xù)靜滴600 mg/m²，滴注時間22 h；治療14 d后暫停1周。對照組在FOLFOX方案基礎(chǔ)上早餐前口服鹽酸安羅替尼膠囊，12 mg/次，1次/d，連續(xù)服藥2周，停藥1周。治療組在對照組治療的基礎(chǔ)上靜脈注射注射用卡瑞利珠單抗，3 mg/kg，間隔≥30 min后進(jìn)行FOLFOX方案，1次/3周。以21 d為1個周期，兩組患者至少完成2個周期。觀察兩組的臨床療效，比較兩組的血清生化指標(biāo)、腫瘤標(biāo)志物水平。結(jié)果 治療后，治療組的疾病控制率（DCR）明顯高于對照組（P＜0.05），但兩組的總有效率（ORR）差異無統(tǒng)計學(xué)意義。治療后，兩組血清丙氨酸氨基轉(zhuǎn)移酶（ALT）、天冬氨酸氨基轉(zhuǎn)移酶（AST）、總膽紅素（TBIL）、凝血酶原時間（PT）水平均顯著降低，白蛋白（ALB）水平顯著升高（P＜0.05）；且治療組血清ALT、AST、TBIL、PT水平顯著低于對照組，ALB水平顯著高于對照組（P＜0.05）。治療后，兩組患者的血清α-L-巖藻糖苷酶（AFU）、甲胎蛋白（AFP）、癌胚抗原（CEA）、糖類抗原199（CA199）水平均明顯降低（P＜0.05）；治療組血清AFU、AFP、CEA、CA199水平均低于對照組（P＜0.05）。結(jié)論 注射用卡瑞利珠單抗聯(lián)合鹽酸安羅替尼膠囊和FOLFOX方案治療晚期肝癌患者療效確切，可提高疾病控制率，改善生化指標(biāo)和血清腫瘤標(biāo)志物水平，且安全性良好。

Objective To observe the clinical effect of Camrelizumab for injection combined with Anlotinib Hydrochloride Capsules and FOLFOX regimen in treatment of advanced liver cancer. Methods Patients (126 cases) with advanced liver cancer in the Second Affiliated Hospital of Hainan Medical University and the First Affiliated Hospital of Hainan Medical University from January 2018 to December 2015 were randomly divided into control and treatment groups, and each group had 63 cases. Patients in two groups were given FOLFOX regimen:On the first day, oxaliplatin for injection, 85 mg/m² added into 5% glucose injection 250 mL, was injected intravenously for 2 h. On the first and second day, Calcium Folinate for injection was injected intravenously for 2 h, 200 mg/m² added into 5% glucose injection 250 mL. On the first and second day, Fluorouracil Injection was injected intravenously 400 mg/m², while continuous intravenous drip of 600 mg/m² for 22 h. After 14 d of treatment, it was suspended for 1 week. Patients in the control group were po administered with Anlotinib Hydrochloride Capsules before breakfast on the basis of FOLFOX regimen, 12 mg/time,once daily. The drug was taken continuously for 2 weeks, and stopped for 1 week. Patients in the treatment group were iv administered with Camrelizumab for injection on the basis of the control group, 3 mg/kg, and FOLFOX scheme shall be carried out after an interval of ≥ 30 min, once every 3 weeks. A cycle had 21 d, and patients in two groups were treated for 2 cycles. After treatment, the clinical efficacies were evaluated, and the serum levels of biochemical indexes and serological tumor markers in two groups were compared. Results After treatment, the DCR in the treatment group was significantly higher than that in the control group (P < 0.05), but there was no significant difference in the ORR between two groups. After treatment, the serum levels of ALT, AST, TBIL, and PT were significantly decreased, but the level of ALB were significantly increased (P < 0.05). The serum levels of ALT, AST, TBIL, and PT in the treatment group were lower than those in the control group, but the level of ALB was higher than those in the control group (P < 0.05). After treatment, the serum levels of AFU, AFP, CEA, and CA199 in two groups were significantly decreased (P < 0.05), and the serum levels of AFU, AFP, CEA, and CA199 in the treatment group were lower than those in the treatment group (P < 0.05). Conclusion Camrelizumab for injection combined with Anlotinib Hydrochloride Capsules and FOLFOX regimen has clinical curative effect in treatment of advanced liver cancer, can improve the disease control rate, biochemical indexes, and serum tumor markers, with good safety.

R975

海南省自然科學(xué)基金面上項目(821MS0833)