阿帕替尼治疗化疗失败的转移性结直肠癌近期疗效及预后分析

  目的  评价阿帕替尼单药或联合化疗治疗转移性结直肠癌的近期疗效及耐受性。  方法  选取2016年1月至2017年12月唐山市人民医院收治的化疗失败的转移性结直肠癌患者23例，病理均经肠镜或手术证实，术后按结直肠癌诊疗规范行化疗，一线或二线化疗进展后进入阿帕替尼单药或联合化疗。单药阿帕替尼组16例，口服阿帕替尼联合化疗组7例，前3个月剂量250~500 mg，每个月评价可测量病灶，3个月以后每3个月应用CT评价疗效，评估阿帕替尼治疗的有效性及不良反应。  结果  所有患者中，无完全缓解（complete response，CR），部分缓解（partial response，PR）9例，病情稳定（stable disease，SD）7例，疾病进展（progressive disease，PD）7例，客观缓解率（overall response rate，ORR）为39.13%，疾病控制率（disease control rate，DCR）为69.56%，疾病无进展生存时间（progressionfree survival，PFS）为1~19.0个月，中位PFS为5.0个月。单药阿帕替尼组无CR，PR 5例，SD 5例，PD 6例，ORR为31.25%，DCR为62.50%，中位PFS为4.5个月。阿帕替尼联合化疗组无CR，PR 4例，SD 2例，PD 1例，ORR为57.10%，DCR为85.70%，中位PFS为12.0个月。Log-Rank单因素分析显示，同步化疗、阿帕替尼剂量、LDH升高、低蛋白血症及疗效评价与PFS相关（均P < 0.05）；同步化疗、阿帕替尼剂量、血红蛋白降低、CD4+淋巴细胞下降及疗效评价与OS相关（均P < 0.05）。Cox回归多因素分析显示，LDH升高为PFS的独立影响因素，上述因素与OS差异无统计学意义（P>0.05）。两组患者不良反应以轻度高血压、蛋白尿、手足综合征为主，差异无统计学意义（均P>0.05）。  结论  阿帕替尼联合化疗可改善化疗失败的转移性结直肠癌患者PFS，可作为转移性结直肠癌治疗的一种有效方法。 

Efficacy of apatinib in metastatic colorectal cancer patients with chemotherapy failure and prognostic analysis

  Objective  To evaluate the short-term efficacy and side effects of apatinib administered alone or in combination with chemotherapy for the treatment of metastatic colorectal cancer.  Methods  The medical records of 23 cases with metastatic colorectal carcinoma, who were treated at Tangshan People's Hospital from January 2016 to December 2017, were retrospectively reviewed. The diagnoses of all the patients were confirmed by microscopy or surgery reports. First-or second-line chemotherapy was administered on the basis of the diagnosis and treatment guidelines for colorectal cancer. After progressive disease was noted in the condition, apatinib was administered as a single drug or in combination with chemotherapy. Sixteen patients received apatinib alone and 7 received apatinib combined with chemotherapy. The dose of apatinib varied from 250 mg to 500 mg. Computed tomography was performed to evaluate the treatment efficacy monthly in the first 3 months, and every 3 months after that. The efficacy and toxicity of apatinib were also evaluated in this study. The Kaplan-Meier method was used to calculate the overall survival rate. The Cox regression model was used for multivariate prognostic analysis.  Results  Analyzing all patients as one group, none of them achieved complete response (CR), 9 of them achieved partial response (PR), 7 cases had stable disease (SD) and 7 cases had progressive disease (PD), overall response rate (ORR) was 39.13%, disease control rate (DCR) was 69.56%, progression-free survival (PFS) ranged from 1 to 19 months, and median PFS was 5 months. In the apatinib group, there were 0 cases of CR, 5 cases of PR, 5 cases of SD, 6 cases of PD, ORR was 31.25%, DCR was 62.5%, and median PFS was 4.5 months. In the apatinib combined chemotherapy group, there were 0 cases of CR, 4 cases of PR, 2 cases of SD and 1 case of PD, with ORR of 57.1%, DCR of 85.7% and median PFS of 12.0 months. Concurrent chemotherapy, apatinib dose, lactate dehydrogenase elevation, hypoalbuminemia, and efficacy evaluation were the main factors contributing to patients' PFS (P < 0.05, respectively). Cox regression multivariate analysis showed that lactate dehydrogenase elevation was an independent factor of PFS. Single-factor analysis of Log-rank test showed that concurrent chemotherapy, apatinib dose, hemoglobin reduction, CD4+ lympho-cyte decline, and therapeutic effect evaluation were correlated with overall survival (P < 0.05, respectively). Cox regression multivariate analysis also showed that there was no statistical significance with respect to overall survival. The toxicity and side effects of the two groups were mainly mild hypertension, proteinuria, and hand-foot syndrome, with no statistical difference.  Conclusions  Apatinib combined with chemotherapy can improve PFS of metastatic colorectal cancer patients with failed chemotherapy, and can be used as an effective method for the treatment of metastatic colorectal cancer.