骨与软组织肉瘤伴肺转移患者应用阿帕替尼联合化疗的临床疗效

摘要

Objective To compare the clinical efficacy and drug safety between oral apatinib combined with conventional chemotherapy and conventional chemotherapy alone for the treatment of osteosarcoma and soft tissue sarcoma patients with pulmonary metastasis. Methods Thirty?three osteosarcoma and soft tissue sarcoma patients with pulmonary metastasis who were treated in the Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University from January 2015 to December 2017 were enrolled in this study. Patients with osteosarcoma received methotrexate, adriamycin (ADM), cisplatin (CDDP), ifosfamide (IFO) sequential regimen; patients with soft tissue sarcoma were treated with IFO and ADM regimen. Eighteen of these patients received an additional oral dose of apatinib. The patients were followed up regularly for changes in primary tumors and metastases, adverse reactions and prognosis. Results Before treatment, the maximum diameter of pulmonary metastases in patients of apatinib group and routine treatment group were ( 4.46 ± 1.70) cm and ( 4.53 ± 2.00) cm, respectively, without significant difference ( P＝0.909). After treatment, the maximum diameter of pulmonary metastases in patients of apatinib group was (1.46 ± 1.39) cm, significantly smaller than ( 3.02 ± 1.20) cm of routine treatment group (P＝0.002). After treatment, the maximum diameter of the primary lesions in the apatinib group and the conventional treatment group median decreased 0.31 cm and 0.12 cm, respectively, without significant difference ( P＝0.542). After treatment, the maximum diameter of the lung metastases in the apatinib group median decreased 0.59 cm, significantly more than 0.18 cm of the conventional treatment group (P＝0.027). The median progression?free survival ( PFS) was 9.4 months in the 33 patients. The median PFS was 9.6 months and 8.3 months in the apatinib group and the conventional treatment group, respectively, without significant difference (P＝0.593). Specific adverse reactions both occurred in apatinib group and routine treatment group, mainly including oral mucosal reactions and digestive tract reactions (including nausea, vomiting and diarrhea). Conclusions Apatinib can effectively reduce the volume of primary and metastatic lesions in patients with bone and soft tissue sarcoma accompanied by lung metastasis without reducing the survival rate or causing uncontrollable adverse reactions. The safety and clinical efficacy of apatinib are significant.%目的 探讨骨与软组织肉瘤伴肺转移患者应用阿帕替尼联合常规化疗和单纯常规化疗的临床疗效和药物安全性.方法 收集2015年1月至2017年12月就诊于中国医科大学肿瘤医院的33例骨与软组织肉瘤伴肺转移患者的临床资料.骨肉瘤患者接受甲氨蝶呤、阿霉素、顺铂和异环磷酰胺序贯方案,软组织肉瘤接受阿霉素+异环磷酰胺联合方案.化疗联合阿帕替尼治疗的患者(阿帕替尼组)18例,常规化疗治疗的患者(常规治疗组) 15例.研究患者的原发灶及转移灶变化、不良反应和预后情况.结果 接受治疗前,阿帕替尼组和常规治疗组患者的肺部转移灶最大直径分别为(4.46±1.70)cm和(4.53±2.00)cm,差异无统计学意义(P＝0.909);治疗后,阿帕替尼组和常规治疗组患者的肺部转移灶最大直径分别为( 1.46 ± 1.39) cm 和( 3.02 ± 1.20) cm,差异有统计学意义( P＝0.002).接受治疗后,阿帕替尼组和常规治疗组患者原发灶最大直径缩小的中位数分别为0.31 cm和0.12 cm,差异无统计学意义(P＝0.542);接受治疗后,阿帕替尼组和常规治疗组患者肺部转移灶最大直径缩小的中位数分别为0.59 cm和0.18 cm,差异有统计学意义(P＝0.027). 33例患者的中位无进展生存时间(PFS)为9.4个月.阿帕替尼组和常规治疗组患者的中位PFS分别为9.6个月和8.3个月,差异无统计学意义(P＝0.593).阿帕替尼组和常规治疗组患者对于化疗均产生了一定程度的不良反应,其中最主要的不良反应为口腔黏膜反应和消化道反应(包括恶心呕吐和腹泻).结论 阿帕替尼可在不降低患者的生存率、不良反应可控的情况下,有效缩小骨与软组织肉瘤伴肺转移患者的原发灶和转移灶体积,药物安全性和临床疗效显著.