应用阿帕替尼治疗进展期软组...肉瘤的临床效果与安全性评估_叶挺.pdf

骨科临床与研究杂志 2023 年 3 月第 8 卷第 2 期J Clin Orthop es，March 2023，Vol8，No2DOI:1019548/j2096-269x 202302005作者单位:430022 武汉，华中科技大学同济医学院附属协和医院肿瘤中心通信作者:陈静，E-mail:chenjingunion163 com骨肿瘤诊治应用阿帕替尼治疗进展期软组织肉瘤的临床效果与安全性评估叶挺李天宇范丽张洁莹陈静【摘要】目的评估阿帕替尼对进展期软组织肉瘤患者的临床疗效与安全性。方法对 2017 年1 月至 2019 年 8 月华中科技大学同济医学院附属协和医院肿瘤中心应用阿帕替尼单药治疗的进展期软组织肉瘤患者 54 例的临床资料进行回顾性分析。其中男 28 例，女 26 例;年龄(38 5 17 9)(6 74)岁;病理亚型包括腺泡状软组织肉瘤(ASPS)10 例、滑膜肉瘤 7 例、平滑肌肉瘤 7 例、横纹肌肉瘤 6 例、未分化小圆细胞肉瘤5 例、未分化多形性肉瘤4 例、脂肪肉瘤4 例、血管肉瘤3 例和其他8 例。以疾病无进展生存期(PFS)、客观缓解率(O)、疾病控制率(DC)和总生存时间(OS)等指标对疗效进行评价;通过观察治疗相关不良反应对药物的安全性进行评价;利用 COX 比例风险模型对发生率较高的非血液学不良反应与疗效相关性进行分析。结果患者总体中位 PFS 为5 8 个月;ASPS、未分化多形性肉瘤和平滑肌肉瘤为治疗优势亚型，中位 PFS 分别为 24 3个月、8 3个月和 7 4个月;1 例(1 8%)患者达到完全缓解，10 例(18 5%)达到部分缓解，34 例(63 0%)达到疾病稳定;O 为 20 4%(11 例/54 例)，DC为 83 3%(45 例/54 例)。中位 OS 为 9 个月。最常见的血液学不良反应是白细胞减少(22 例/54 例，40 7%)和贫血(21 例/54 例，38 9%)，最常见的非血液学不良反应是手足综合征(30 例/54 例，55 6%)、甘油三脂升高超过 1 mmol/L(33 例/44 例，75%)、胆红素升高(26 例/54 例，48 1%)、高血压(25 例/54 例，46 3%)和胆固醇升高(25 例/44 例，56 8%)，其中多为 级。发生手足综合征与未发生手足综合征患者的中位 PFS 分别为 12 5 个月和 3 4 个月，差异有统计学意义(P 0 001);发生腹泻与未发生腹泻患者的中位 PFS 分别为 35 0 个月和 4 5 个月，差异有统计学意义(P 0 001);发生高脂血症且胆固醇升高超过 1 5 mmol/L 与未达上述标准患者的中位 PFS 分别为 24 3 个月和 4 0 个月，差异有统计学意义(P=0 004);发生高血压和蛋白尿的患者有 PFS 延长的趋势;口腔溃疡、甘油三脂升高超过 1 mmol/L 和胆红素升高与 PFS 无显著相关性。结论应用阿帕替尼治疗进展期软组织肉瘤患者可获得令人满意的临床效果，不良反应基本可控，且部分不良反应可能作为疗效预测指标。【关键词】肉瘤;肿瘤，结缔和软组织;血管生成抑制剂;药物疗法;治疗结果;药物相关性副作用和不良反应;阿帕替尼基金项目:北京市希思科临床肿瘤学研究基金(Y-H2016-158);华中科技大学同济医学院研究型临床医师资助计划Efficacy and safety of apatinib in the treatment of advanced soft tissue sarcomaYe Ting，Li Tianyu，Fan Li，Zhang Jieying，Chen Jing Cancer Center of Union Hospital Affiliated to Tongji Medical College ofHuazhong University of Science and Technology，Wuhan 430022，ChinaCorresponding author:Chen Jing，E-mail:chenjingunion163 com【Abstract】ObjectiveTo evaluate the efficacy and safety of apatinib in the treatment of advanced softtissue sarcoma MethodsClinical data of 54 patients with advanced soft tissue sarcoma received apatinib asmonotherapy in Cancer Center of Union Hospital Affiliated to Tongji Medical College of Huazhong University ofScience and Technology from January 2017 to August 2019 were analyzed retrospectively There were 28 malesand 26 femals with an age of(38 5 17 9)(6-74)years The pathological subtypes included alveolar soft partsarcoma(ASPS)(n=10)，synovial sarcoma(n=7)，leiomyosarcoma(n=7)，rhabdomyosarcoma(n=6)，19骨科临床与研究杂志 2023 年 3 月第 8 卷第 2 期J Clin Orthop es，March 2023，Vol 8，No2undifferentiated small round cell sarcoma(n=5)，undifferentiated pleomorphic sarcoma(n=4)，liposarcoma(n=4)，angiosarcoma(n=3)and the others(n=8)The primary end point was progression-free survival(PFS)，and the secondary end points were objective response rate(O)，disease control rate(DC)，overall survival(OS)and adverse effectsesultsThe median PFS of was 5 8 monthsASPS，undifferentiated pleomorphic sarcoma and leiomyosarcoma were the dominant subtypes with the median PFS was24 3 months，8 3 months and 7 4 months，respectively Of the all patients，one(1 8%)achieved completeresponse，10(18 5%)achieved partial response and 34(63 0%)achieved disease stability The O andthe DC were 20 4%(11/54)and 83 3%(45/54)，respectively The median OS was 9 months The mostcommon hematological adverse reactions were leukopenia(22/54，40 7%)and anemia(21/54，38 9%)Themost common non-hematological adverse reactions were hand-foot syndrome(30/54，55 6%)，elevatedtriglycerides exceeding 1 mmol/L(33/44，75%)，elevated bilirubin(26/54，48 1%)，hypertension(25/54，46 3%)and elevated cholesterol(25/44，56 8%)The median PFS of patients with hand-foot syndrome andwithout hand-foot syndrome was 12 5 and 3 4 months，respectively(P 0 001)The median PFS of patientswith diarrhea and without diarrhea was 35 0 and 4 5 months(P 0 001)，respectively The median PFS ofpatients with elevated cholesterol exceeding 1 5 mmol/L and those who did not meet the above criteria were24 3 and 4 months(P=0 004)，respectively Patients with hypertension and albuminuria tended to haveprolonged PFSOral ulcers，elevated triglycerides exceeding 1 mmol/L and elevated bilirubin were notsignificantly correlated with PFS ConclusionThe efficacy of apatinib in the treatment of advanced soft tissuesarcoma is satisfactory and the adverse reactions were tolerated，moreover the occurrence of some adversereactions may be used as predictors of efficacy【Key words】Sarcoma;Neoplasms，connective and soft tissue;Angiogenesis inhibitors;Drug therapy;Treatment outcome;Drug-related side effects and adverse reactions;ApatinibFund program:Beijing CSCO Clinical Oncology esearch Foundation(Y-H2016-158);FundingProgram for esearch Clinicians of Tongji Medical College，Huazhong University of Science and Technology软组织肉瘤是一类发生于除软骨以外全身各结缔组织的恶性肿瘤。中国软组织肉瘤发病率为(2 4 5 0)/10 万1。40%60%的软组织肉瘤患者会出现肿瘤转移，肿瘤转移患者 5 年生存率约为20%2-3。除部分对化学治疗极不敏感的肉瘤如腺泡状软组织肉瘤(alveolar soft part sarcoma，ASPS)和透明细胞肉瘤等患者外，进展期软组织肉瘤患者的一线治疗是化学治疗，二线治疗没有标准方案，可以选择化学治疗或抗血管生成小分子靶向药物治疗4。具有代表性的抗血管生成小分子靶向药物培唑帕尼于 2012 年 4 月 26 日在美国获批准用于除脂肪肉瘤和胃肠道间质瘤外的晚期软组织肉瘤患者的二线治疗;国产药安罗替尼于 2019 年 7 月 5 日在中国获批准用于 ASPS、透明细胞肉瘤以及既往至少接