阿帕替尼治疗晚期难治性软组织肉瘤28例的疗效和安全性

摘 要：［目的］ 评价阿帕替尼治疗晚期难治性软组织肉瘤疗效及不良反应。［方法］ 2015年5月至2017年5月晚期难治性软组织肉瘤28例患者口服阿帕替尼500mg,每日1次,28d为1个疗程,直至疾病进展或无法耐受的毒副反应。采用RECISIT1.1评价疗效,CTCAE4.03评价不良反应。［结果］ 28例患者中,PR 6例（21.4%）,SD 17例（60.7%）,PD 5例（17.9%）,ORR为24.1%,DCR为82.1%。患者的中位生存期为3.7个月（95%CI：2.9~4.4）,中位总生存期为9.1个月（95%CI：7.3~11.0）。3~4级不良反应较多的血液学毒性为白细胞减少和中性粒细胞减少,发生率均为10.7%,非血液学毒性为手足综合征（14.2%）、高血压（7.1%）和蛋白尿（7.1%）。［结论］ 阿帕替尼治疗晚期难治性软组织肉瘤体现出一定的疗效,且不良反应可耐受。     

阿帕替尼治疗晚期滑膜肉瘤1例

滑膜肉瘤(synovial sarcoma,SS)是一种起源于肌肉、滑囊、肌腱或筋膜且高度恶性的间叶源性恶性肿瘤,约占原发性恶性软组织肿瘤的 10％ [1] . SS 恶性程度高,早期易发生远隔器官转移,最常见为肺转移,目前治疗以手术为主,术后辅以放化疗,但对于初次诊断时已为晚期 SS(出现远隔器官转移)的治疗,目前仍...     

甲磺酸阿帕替尼治疗晚期转移性腺泡状软组织肉瘤1例

<正>0 引言腺泡状软组织肉瘤(alveolar soft part sarcoma ASPS)是一种十分罕见的软组织肉瘤，常见于青、少年，发病率仅占所有软组织肉瘤的1%^[1]。ASPS的特点是肿瘤生长缓慢，因症状不明显而常被忽视。与其他类型肉瘤不同的是，ASPS极易发生转移，如肺转移(90%)、骨转移(26%)、脑转移(11%～19%)和其他部位转移(24%)^[1]。治疗上以手术治疗为主，术后辅以放化疗，对于化疗不敏感，靶向药物联合化疗的综合治疗国内外较罕见。2013年7月我科收治1例大腿ASPS手术后复发伴双肺转移的患者，全身化疗后出现颅脑转移，继发癫痫，进而局部伽马刀治疗等一系列治疗无效，     

阿帕替尼治疗晚期胃癌的临床疗效观察

目的:探讨阿帕替尼治疗晚期胃癌患者的临床疗效和安全性。方法:回顾性分析我院2016年1月至2017年2月接受阿帕替尼治疗的28例化疗失败的胃癌患者,给予阿帕替尼500 mg/d,直至患者出现疾病进展或不可耐受的不良反应,分析其疗效和安全性。结果:阿帕替尼治疗晚期胃癌的有效率（RR）为10.7%,疾病控制率（DCR）为42.8%,中位无进展生存时间（PFS）为3.6个月,中位总生存时间（OS）为5个月,患者耐受性良好,常见的不良反应为高血压、手足综合征和蛋白尿。结论:阿帕替尼治疗二线或以上化疗失败的晚期胃癌具有良好的疗效和安全性。     

甲磺酸阿帕替尼三线或三线以上治疗晚期胃腺癌的临床观察

目的 探讨甲磺酸阿帕替尼三线或三线以上治疗晚期胃腺癌的临床疗效和安全性。方法 回顾性分析2014年12月至2016年1月接受过二线及二线以上化疗方案治疗失败的20例晚期胃腺癌患者,给阿帕替尼500 mg／天口服,持续用药至肿瘤进展或出现不可耐受的不良反应。结果 20例胃腺癌患者的有效率（RR）和疾病控制率（DCR）分别为10.0％和40.0％,中位无进展生存时间（PFS）和中位总生存时间（OS）分别为2.7个月和4.3个月。患者耐受性良好,常见的毒副反应为1～3级高血压、手足综合征和蛋白尿。结论 对于接受过二线及二线以上化疗方案治疗失败的晚期胃腺癌患者,阿帕替尼具有良好的疗效和安全性。     

阿帕替尼治疗晚期难治性三阴性乳腺癌的临床疗效观察

  目的  评价阿帕替尼治疗晚期难治性三阴性乳腺癌的临床疗效及不良反应。  方法  回顾性分析2015年7月至2016年11月就诊于天津医科大学肿瘤医院,经病理学确诊为晚期三阴性乳腺癌,既往接受过两线以上化疗后疾病进展(progressive disease,PD)、服用阿帕替尼500 mg/d治疗的8例患者临床资料,所有患者均在接受2个周期以上治疗后评价疗效,观察PD时间、有效率、临床获益率及不良反应。  结果  8例患者共接受平均4个周期的治疗,经过中位随访时间为8 (4~11) 个月,其中部分缓解(partialremission,PR) 4例,疾病稳定(stable disease,SD) 3例,PD 1例;疾病控制率(disease control rate,DCR)为87.5%(7/8),客观缓解率(objective response rate,ORR)为50% (4/8),平均无进展生存期(progression free survival,PFS)为4.2个月。不良反应为手足综合征(3/8)、骨髓抑制(4/8)、高血压(2/8)、蛋白尿(3/8)、咯血(1/8)、恶心(2/8)、乏力(2/8) 等。  结论  阿帕替尼在三阴性乳腺癌的治疗中可获得一定的疗效及生存获益,且安全性好,不良反应可控。      

甲磺酸阿帕替尼治疗晚期肝内胆管癌的临床观察

目的观察和评价甲磺酸阿帕替尼治疗晚期肝内胆管癌的疗效和安全性。方法回顾性分析2018年5月至2019年5月接受甲磺酸阿帕替尼治疗的15例晚期肝内胆管癌患者,均口服甲磺酸阿帕替尼(250 mg/日,4周为1个周期),其中一线治疗1例,二线治疗6例,其余为三线及以上治疗。采用RECIST 1.1版和NCI CTC 4.0版标准分别评价近期疗效和不良反应。生存分析采用Kaplan-Meier法。结果随访截止于2019年11月1日,失访1例,13例可评价近期疗效和无进展生存时间(PFS),14例可评价总生存时间(OS)。中位治疗时间为13周。13例患者中获PR 1例,SD 8例,PD 4例;有效率为7.7%,疾病控制率为69.2%;中位PFS为75天,中位OS为294天。主要不良反应包括高血压、手足皮肤反应、口腔溃疡、腹泻和蛋白尿等,以1~2级为主,3级不良反应为2例高血压。结论甲磺酸阿帕替尼治疗晚期肝内胆管癌效果较好,且耐受性良好。     

甲磺酸阿帕替尼治疗晚期恶性肿瘤的疗效观察

目的探讨甲磺酸阿帕替尼治疗晚期恶性肿瘤的临床效果。方法选取晚期恶性肿瘤患者257例作为研究对象,所有患者均有行二线或二线以上治疗史。对照组患者进行最佳支持治疗,观察组在最佳支持治疗基础上应用甲磺酸阿帕替尼片进行治疗。评价疗效、生存期及观察药物毒副作用。结果观察组患者CEA、CYFRA21-1、VEGF、MMP-9水平低于对照组,有统计学意义(P<0.05)。观察组治疗有效率高于对照组,2组有统计学差异(P<0.05)。观察组主要毒副作用为高血压、骨髓抑制、乏力、手足综合征、蛋白尿等反应。结论甲磺酸阿帕替尼治疗晚期恶性肿瘤的临床效果较好,不良反应较轻,临床应用价值较高,值得推荐。     

Efficacy and safety of apatinib monotherapy in advanced bone and soft tissue sarcoma: An observational study

Sarcomas are rare but malignant tumors with high risks of local recurrence and distant metastasis. Anti-angiogenic therapy is a potential strategy against un-controlled and not-organized tumor angiogenesis. We aimed to assess the safety and efficacy of apatinib, an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, in patients with advanced sarcoma. Thirty-one patients who received initial apatinib between September 2015 and August 2016 were retrospectively reviewed. Among them, 19 (61.3%) patients were heavily pretreated with two or more lines of cytotoxic chemotherapy. Apatinib was given at a start-dose of 425 mg qd. During therapy, 9 (29.0%) patients required dose interruption and 7 (22.6%) needed dose reduction, and the mean dosage of apatinib was 372.9 ± 68.4 mg/day. In the study cohort, one patient was treated as adjunctive therapy and 6 patients stopped treatment before radiographic response assessment. Thus, 24 patients were eligible for tumor response evaluation. The objective response rate was 33.3% and clinical benefit rate was as high as 75.0%. The progression free survival was 4.25 (95% confidence interval [CI], 2.22–5.11) months, whereas the overall survival was 9.43 (95% CI, 6.64–18.72) months. Compared with other histological subtypes, leiomyosarcoma did not show significant survival benefits. Most of the adverse events (AEs) were at grade 1 or 2. The main grade 3 AEs were hypertension (6.5%), hand foot skin reaction (6.5%), and diarrhea (3.2%). In conclusion, apatinib showed promising efficacy and acceptable safety profile in metastatic or recurrent sarcoma, giving rationale clinical evidence to conduct clinical trials.     

Chemotherapy of advanced bone and soft tissue sarcoma

The primary site of metastasis of bone and soft tissue sarcoma is the lung. Control of these sarcomas depends upon the prevention and treatment of their pulmonary metastasis. The introduction of a chemotherapy consisting mainly of Adriamycin and high-dose methotrexate dramatically improved the prognosis of osteosarcoma. However the effectiveness of chemotherapy has not yet been duplicated in soft tissue sarcomas except some childhood sarcomas. We analyzed the clinical data for pulmonary metastasis of osteosarcomas and soft tissue sarcomas. Based on these analyses, we tried to clarify the nature of pulmonary metastasis of these sarcomas and to evaluate its response to treatment, that this would yield clues to future treatment of these sarcomas.     

Olaratumab for the treatment of advanced soft tissue sarcoma

Introduction: Olaratumab, a human monoclonal antibody against platelet derived growth factor receptor alpha (PDGFR- α), is the first drug that in combination with doxorubicin for the treatment of patients with advanced/metastatic soft tissue sarcoma (STS) that has showed an improved overall survival compared to doxorubicin alone. These initial results are exciting and have the potential to change the landscape of treatment for patients with STS.

Areas covered: This article reviews the development of olaratumab for oncology use by reviewing articles in PubMed for ‘platelet derived growth factor’ and ‘receptor’ and ‘soft tissue sarcoma’. We provide an overview of the published studies to date for olaratumab and specifically the use in soft tissue sarcoma.

Expert commentary: Olaratumab is a well-tolerated drug that, when combined with doxorubicin, has shown an improved overall survival compared to doxorubicin alone and the phase III confirmatory study is eagerly awaited.     

Surgical treatment for bone and soft tissue sarcoma

There are many kinds of wide excision or wide resection, which are methods to remove the tumor with surrounding tissues. The curability of wide resection depends on the range and characteristics of the normal surrounding tissues. The fascia, periosteum and perivascular sheath act as barriers against invasion of tumors. Therefore, evaluation of the surgical margin is essential in surgery for malignancy. Some sarcomas characteristically show invasive growth patterns while others have a discrete border. Causes of the local recurrence are 1) insufficient surgical margin, 2) skip metastasis, 3) tumor thrombus, and 4) lymph node metastasis. The so-called "Safety surgical margin" is the margin that prevents local recurrence due to insufficient surgical treatment. Local recurrence due to other causes can not be treated by surgery alone as chemotherapy is also required. For example, the infiltrative type of malignant fibrous histiocytoma requires a curative procedure. On the other hand, non-infiltrative types of sarcoma or high-grade sarcoma, which are good responders to preoperative treatment, are locally controlled by an adequate wide margin procedure. When the tumor is close to the bone, main vessels and/or nerves, it is sometimes very difficult to preoperatively decide whether or not to sacrifice these important organs. A new surgical method, "In Situ Preparation (ISP)," is a useful method to solve such problems. ISP makes it possible to evaluate the surgical margin without contamination. And additional procedures including alcohol soaking or pasteurization can be achieved according to the surgical margin. Because ISP can prevent overtreatment, the number of our cases that require resection of the nerves or vessels have decreased. After a wide resection, there have been many possible complications, including infection, deep venous thrombosis, loosening of prosthesis, skin necrosis, and arterial occlusion. Once postoperative complications occur, patients must remain in the hospital for a long time. To prevent this, the preservation of normal tissue, meaning reduction of surgical margin, is important.     

沙利度胺治疗晚期软组织肉瘤的临床观察

目的 评价沙利度胺单药治疗晚期软组织肉瘤的疗效、不良反应及对患者生活质量的影响。方法 22例二线方案化疗失败的晚期软组织肉瘤患者口服沙利度胺,每日100mg晚睡前顿服,1周后加量至每日200mg,维持治疗至疾病进展,同时每日口服阿斯匹林75mg。每2个月评价疗效、毒副反应,参照Karnofsky评分评价患者生活质量（QOL）。结果 2例获得PR（9.1％）,4例SD（18.2％）,疾病控制率（DCR）为27.3％;中位无进展生存期为1个月,中位总生存期为5个月;3例（13.6%）生活质量改善,5例（22.7%）稳定。主要不良反应为便秘、疲乏、嗜睡,多为1～2级,其他不良反应少见。结论 单药沙利度胺治疗软组织肉瘤具有一定疗效,可提高部分患者的生活质量。     

术中置管近距离放疗在骨与软组织肉瘤治疗中的应用

目的分析术中置管近距离放疗在骨与软组织肉瘤综合治疗中应用的疗效和毒性。方法163例骨与软组织肉瘤的病例，其中59例采用手术＋化疗＋外照射，另外104例采用手术＋化疗＋近距离放疗＋夕h照射的综合治疗方法。结果采用近距离放疗的一组患者有较好的疗效和较低的毒性。结论术中置管近距离放疗在骨与软组织肉瘤的综合治疗中有较好临床应用价值．．     

重组人血小板生成素二级预防阿帕替尼联合化疗治疗晚期骨与软组织肉瘤患者血小板减少症的疗效分析

目的评价重组人血小板生成素(rhTPO)二级预防阿帕替尼联合吉西他滨+多西他赛(GT)方案化疗致血小板减少的有效性。方法 90例在一线治疗过程中出现血小板减少,拟行阿帕替尼联合GT方案治疗的晚期骨与软组织肉瘤患者,随机分为3组(1∶1∶1), 30例空白对照组患者不给予rhTPO二级预防;治疗组1(n=30):GT化疗第1～5天皮下注射rhTPO 300 U/kg/d,每日1次;治疗组2:GT化疗第1、3、5、7、9天皮下注射TPO 300 U/kg/d,隔日1次。动态记录患者化疗后血小板变化及不良反应情况。结果对照组、治疗组1和治疗组2发生1～2级血小板减少人数分别为12、6和5例,3级血小板减少人数分别为8、3和2例,对照组血小板减少的患者比例显著高于2个治疗组(P<0.05);对照组、治疗组1和治疗组2化疗第14天时的血小板绝对值分别为(56.86±41.49)×10⁹/L、(84.60±37.31)×10⁹/L和(85.67±39.67)×10⁹/L,对照组显著低于2个治疗组(P<0.05);对照组、...     

Complex treatment of locally advanced soft tissue sarcoma of the limbs

The experience of treatment of 40 patients with locally-advanced soft tissue sarcoma of the limbs. Treatment included preoperative chemoradiotherapy in combination with electromagnetic hyperthermia. As a result, 38 (95%) patients showed marked response which allowed radical limb-saving surgery whereas in 2 (5%) amputation was performed. Adjuvant chemotherapy was used for anaplastic tumors. Five-year survival rate was 64.7 +/- 6.7%.     

异环磷酰胺联合表阿霉素治疗晚期软组织肉瘤27例疗效分析

目的观察异环磷酰胺（IFO）联合表阿霉素（EPI）方案治疗晚期软组织肉瘤（ASTS）的疗效与安全性。方法采用IFO＋EPI方案治疗ASTS 27例。IFO 6g/m^2,分d1～3静脉滴入或96 h持续静脉点滴;EPI 90 mg/m^2,分d1～3（或96 h持续静脉点滴）,21 d为1个周期。本组中位化疗周期数为3个（2～5个）。结果CR 0例,PR 5例,SD 13例,PD 9例,全组总有效率18.5%,临床获益率为66.7%,1年生存率为37.0%,2年生存率为11.1%。其中5例PR患者均为一线治疗,一线治疗有效率为23.8%（5/21）。主要毒性反应为骨髓抑制及胃肠道反应。结论EPI联合IFO治疗ASTS,使用方便、疗效确切、毒性反应较轻,该方案是ASTS有效解救治疗方案。