阿帕替尼单药治疗进展期非小细胞肺癌疗效观察

目的探索阿帕替尼单药治疗进展期非小细胞肺癌(NSCLC)的疗效和安全性。方法选取进展期NSCLC患者共65例。随机分为对照组(n=30),行多西他赛化疗;治疗组(n=35),行阿帕替尼治疗。对两组患者进行疗效和毒副反应评价。结果对照组完全缓解0例,部分缓解3例,稳定11例,进展16例,治疗组完全缓解0例,部分缓解6例,稳定17例,进展12例,P0.05。阿帕替尼毒副反应可控,较对照组毒副反应发生率显著降低。结论阿帕替尼对进展期NSCLC具有一定疗效和可耐受的毒性。     

吉非替尼单药治疗老年晚期非小细胞肺癌患者的临床观察

目的观察吉非替尼单药治疗老年晚期非小细胞肺癌（NSCLC）患者的有效性与安全性。方法北京协和医院呼吸科收治的63例老年晚期NSCLC患者接受吉非替尼250mg／d治疗,观察患者的一般情况,记录不良反应,并进行疗效评价。中位生存期采用Kaplan-Meier方法计算,不同因素分层生存期比较采用多因素Cox回归分析。结果不良反应一般较轻（1度或2度）,停药后可缓解,最常见的不良反应为皮疹76．8％（43／56）和腹泻35．7％（20／56）。疾病客观有效率、稳定率分别为25．4％、55．6％。所有患者的中位生存期为15．3个月（11．8～18．8个月）。1年生存率为53％。多因素Cox回归分析显示,ECOG体能评分2分以上、有肝脏转移、有胸腔积液、疾病于化疗后复发、吉非替尼治疗的客观疗效是影响生存期的因素。化疗后疾病稳定的23例患者与化疗后疾病进展的24例患者接受吉非替尼治疗后,其两者的生存期比较差异有统计学意义。治疗后出现皮疹与客观疗效相关。结论老年晚期NSCLC患者对吉非替尼的治疗能很好耐受,可延长患者的生存时间。     

阿帕替尼治疗晚期胃癌的临床疗效及预后

目的:探讨阿帕替尼用于二线及二线以上治疗失败的晚期胃癌患者的临床疗效分析及预后因素研究.方法:研究对象为2014-10/2015-08曾接受过二线及二线以上治疗失败的60例晚期胃癌患者,均经病理确诊.给予阿帕替尼口服850m g/d,直至疾病进展,观察临床疗效及不良反应发生情况.应用Kaplan-Meier法进行生存分析.结果:根据实体瘤的疗效评定标准(Response Evaluation Criteria in Solid Tumors,RECIST)全部可评价疗效.其中完全缓解(complete response,CR)占0%(0/60),部分缓解(partial response,PR)占3.33%(2/60),疾病稳定(stable disease,SD)占38.33%(23/60),疾病进展(progressive disease,PD)占58.33%(35/60).客观缓解率(CR+PR)为3.33%,疾病控制率(CR+PR+SD)为38.33%(23/60).中位无进展生存期为3.76 mo.甲胎蛋白(a-f e t o p r o t e i n,A F P)阳性胃癌患者的疾病控制以及生存受益优于AFP阴性患者.高血压、骨髓抑制是影响阿帕替尼治疗的最主要的不良反应.结论:阿帕替尼治疗二线及二线以上治疗失败的晚期胃癌仍有较好的疾病控制及生存获益,不良反应可控制,值得临床上广泛应用.     

阿帕替尼治疗老年晚期肝癌的临床效果及安全性

目的探讨阿帕替尼治疗老年晚期肝癌的疗效及安全性。方法收集2018年1月至2018年6月49例老年晚期肝癌患者,接受阿帕替尼单药治疗。按照RECIST1.1标准进行疗效评价,NCI-CTCAE version 4.0评价药物的不良反应并随访生存情况。应用Kaplan-Meier法进行生存分析,Cox回归模型进行多因素分析。结果与治疗前相比,治疗4周后,患者病灶最大直径和及甲胎蛋白水平都降低,差异具有统计学意义(P<0.05)。治疗12周后,患者客观缓解率(CR+PR)和疾病控制率(CR+PR+SD)分别为8.16%(4/49)和77.55%(38/49)。49例老年患者的中位无进展生存期(mPFS)为7.75个月。Cox多因素分析结果表明病灶最大直径和为独立影响因素[HR:1.866,95%CI(2.470~16.916),P=0.000]。不良反应发生率为100%,以1~2级为主。结论阿帕替尼治疗老年晚期肝癌有一定疗效,且不良反应可控,可作为多线治疗失败的老年晚期肝癌患者的一种有效的治疗选择。     

表皮生长因子受体酪氨酸激酶抑制剂一线治疗老年晚期非小细胞肺癌的临床研究

目的观察老年晚期非小细胞肺癌(NSCLC)病人一线应用表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)靶向治疗药物的疗效及安全性。方法选取老年晚期NSCLC病人126例,应用吉非替尼(250mg,1次/d口服)59例,应用厄洛替尼(150 mg,1次/d口服)16例,应用埃克替尼(125 mg,3次/d口服)51例。观察3组病人接受不同EGFR-TKIs治疗的疗效、不良反应及无进展生存期(PFS)。结果 2例不能耐受而中止用药,1例自行放弃治疗,共123例完成治疗。无完全缓解(CR)病例,部分缓解(PR)61例,稳定(SD)33例,进展(PD)29例,有效率(ORR)为49.6%,疾病控制率(DCR)为76.4%。全组病人中位无进展生存期(m PFS)为10.2月。吉非替尼、厄洛替尼、埃克替尼各组间疗效差异无统计学意义(P0.05)。结论老年晚期NSCLC病人应用吉非替尼、厄洛替尼、埃克替尼安全有效,不良反应轻微,均可耐受。     

吉非替尼治疗老年晚期非小细胞肺癌的临床研究

目的 探讨表皮生长因子受体酪氨酸激酶抑制剂吉非替尼治疗老年晚期非小细胞肺癌(NSCLC)的疗效及不良反应. 方法 选择46例≥65岁老年晚期NSCLC患者,吉非替尼250 mg,口服,每日1次,服用至病情进展(PD)或出现不可耐受的不良反应.患者在治疗后每月进行复查. 结果 本组46例均可评价疗效,其中部分缓解(PR)12例(26.09%)、稳定(SD)20例(43.48%)、PD 14例(30.43%).疾病控制率(PR+SD)为69.57%.中位疾病进展时间(TTP)为3.8月,1年生存率为28.26%,肿瘤相关症状改善率为63.33%.常见不良反应为皮疹和腹泻,大部分为Ⅰ、Ⅱ度. 结论 吉非替尼单药治疗老年晚期NSCLC疗效明确,不良反应相对较小,患者耐受性好.     

吉非替尼一线治疗非小细胞肺癌患者的临床观察

目的评价吉非替尼一线治疗非小细胞肺癌（NSCLC）的疗效和安全性。方法 23例NSCLC患者应用吉非替尼250mg/d,直至肿瘤进展或出现不可耐受的不良反应。将患者分为吉非替尼治疗控制组和未控制组,治疗控制组包括完全缓解（CR）、部分缓解（PR）和疾病稳定（SD）;未控制组为疾病进展（PD）,比较两组的临床特点和疗效。结果 23例中完全缓解（CR）0例,部分缓解（PR）12例,疾病稳定（SD）4例,疾病进展（PD）7例,疾病控制率为70%。生存期Kaplan-Meier曲线示：吉非替尼控制组较未控制组有明显的生存优势。COX回归分析示吉非替尼治疗后病情控制状况是患者生存期的影响因素,而非性别、年龄、病理类型、吸烟史。皮疹、腹泻是最主要的不良反应。结论吉非替尼一线治疗NSCLC疗效较好,可明显改善症状、提高生活质量,毒副反应轻。     

替吉奥与阿帕替尼治疗老年晚期胃癌疗效及安全性

目的比较替吉奥与阿帕替尼二线治疗老年晚期胃癌患者的临床疗效及安全性。方法一线治疗失败的老年晚期胃癌患者69例随机分为研究组与对照组,研究组采取单药阿帕替尼方案,对照组采用单药替吉奥,比较两组有效率、无进展生存时间(PFS)、总生存期(OS)及毒副反应。结果研究组客观有效率(RR)为17%,疾病控制率(DCR)为60%,PFS为4.2个月,中位OS为8.0个月;对照组RR为24%,DCR为74%,PFS为4.6个月,OS为7.0个月;两组疗效差异均无统计学意义。两组毒副反应均可耐受,研究组最常见的毒副反应为高血压和手足综合征,对照组最常见的毒副反应为白细胞减少和贫血,没有治疗相关的死亡。结论老年晚期胃癌患者可从阿帕替尼及替吉奥中获益,毒副反应低。阿帕替尼或替吉奥对老年晚期胃癌患者具有较好的临床效果,口服方便,缩短住院时间,可以明显改善患者的生活质量,且不良反应少。     

厄洛替尼治疗吉非替尼失败后晚期非小细胞肺癌的疗效

目的 评价厄洛替尼治疗吉非替尼失败后晚期非小细胞肺癌( NSCLC)的疗效及安全性临床研究.方法 选择12例既往口服吉非替尼有效,但后来又因病情进展而口服厄洛替尼的NSCLC患者,均予厄洛替尼150mg,每日1次口服,1个月后评价疗效及安全性.结果 口服厄洛替尼组12例病人无CR及PR病人,疾病控制率75％(9/12),肿瘤无进展生存期(PFS)4.1个月,症状缓解率75％,主要毒副反应为皮疹、腹泻.结论 对于吉非替尼治疗NSCLC失败后,采用厄洛替尼治疗可延长病人PFS时间,改善病人生存质量.     

安罗替尼治疗表皮生长因子受体野生型老年晚期非小细胞肺癌病人的临床疗效

目的观察盐酸安罗替尼治疗表皮生长因子受体(EGFR)野生型老年晚期非小细胞肺癌(NSCLC)病人的疗效和安全性。方法选择2018年6月至2019年3月我院肿瘤科就诊的EGFR野生型老年晚期NSCLC病人,常规给予安罗替尼12 mg/次,1次/d,连续服药2周,停药1周,即3周为1个疗程。记录病人无进展生存期(PFS)、客观缓解率(ORR)、疾病控制率(DCR)及不良反应发生情况。结果共纳入26例病人,年龄66~85岁,中位年龄74.5岁;一线治疗21例,二线治疗3例,三线治疗2例。截至2019年10月10日,26例病人ORR为11.54%、DCR为76.92%、PFS为5.1个月。常见的不良反应为高血压、手足综合征、疲劳乏力、咯血、甲状腺功能异常等,不良反应经对症处理及安罗替尼暂停、减量后均可控制,未出现药物相关的死亡。结论安罗替尼在EGFR野生型晚期老年NSCLC病人的治疗中,病人的PFS有延长趋势,ORR及DCR较高,不良反应可控。     

白蛋白结合型紫杉醇联合铂类治疗NSCLC临床疗效观察

目的评价白蛋白结合型紫杉醇联合铂类方案一线和二线治疗晚期肺癌(NSCLC)的临床疗效及毒副反应。方法 82例使用白蛋白结合型紫杉醇联合铂类治疗的NSCLC患者,分为A、B两组,计算患者的近期客观反应率(OR)、疾病控制率(RR)、疾病进展时间(TTP)、生存期(OS)、1年生存率;观察患者的毒副反应及耐受性。结果 82例患者总有效率21.95%,疾病控制率73.17%,疾病进展时间(TTP):6.3月。中位生存期:10.3月,1年生存率:36.59%。不良反应可以耐受。结论白蛋白结合型紫杉醇联合顺铂或卡铂方案是治疗晚期肺癌安全有效的化疗方案之一,可以推荐在临床使用。     

阿帕替尼在二线以上小细胞肺癌中的临床应用

目的探讨阿帕替尼应用于二线以上进展期小细胞肺癌的临床疗效、不良反应、影响因素和生存分析。 方法收集二线以上化疗失败的小细胞肺癌患者30例,均给予甲磺酸阿帕替尼片500 mg/次/d口服,28 d为一疗程,有Ⅲ-Ⅳ级不良反应时减量至250 mg/次/d,至疾病进展或药物不良反应无法耐受则停药,观察服药2个疗程的临床疗效,及整个服药期间的不良反应。通过Kaplan-Meier法分析生存情况和影响因素,将有统计学意义的影响因素纳入多因素Cox比例风险模型进行分析。 结果30例患者经过2个疗程评估客观缓解率(ORR)为36.6%,疾病控制率(DCR)为66.6%,中位无疾病进展期(PFS)4.0个月(95%CI 2.864～5.136个月),中位总生存期(OS)6.0个月(95%CI 4.555～7.445个月)。治疗期间主要不良反应为高血压发生率56.6%,蛋白尿发生率33.33%,血小板减少率56.6%,白细胞减少率86.6%,丙氨酸氨基转移酶升高16.6%,胃肠道反应10.0%,疲劳33.3%,手足综合证23.3%,无Ⅳ级以上不良反应。应用Kaplan-Meier法和多因素Cox回归模型分析低钠血症(HR＝3.693,95%CI为1.043～13.082,P＝0.043)、高血压(HR＝0.279,95%CI为0.090～0.869,P＝0.028)是PFS的独立影响因素,低钠血症(HR＝8.675,95%CI为2.284～32.947,P＝0.002)、分期(HR＝4.915,95%CI为1.151～20.978,P＝0.032)、高血压(HR＝0.128,95%CI为0.031～0.537,P＝0.005)是OS的独立影响因素。 结论阿帕替尼应用于二线以上进展期小细胞肺癌存在疗效,不良反应可耐受。治疗前期出现低钠血症及分期较高的患者预后不佳,不良反应出现高血压应用阿帕替尼可能存在生存优势。     

A Case Report of Gastrointestinal Hemorrhage and Perforation During Apatinib Treatment of Gastric Cancer

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which shows good efficacy and safety in clinical trials for chemotherapy-refractory gastric cancer patients. Till now, there is no case report after apatinib came in the market.We presented a 55-year-old Chinese woman with advanced gastric cancer, who received apatinib after failure of second-line chemotherapy. On the 19th day of apatinib administration, she suffered from gastrointestinal hemorrhage. Then, her condition rapidly deteriorated to gastrointestinal perforation. Although the patient received timely medical and surgical treatment, she finally died of septic shock.Although apatinib shows exciting efficacy and good tolerance in phase II and III clinical trials, this novel targeted drug should be prescribed carefully and close clinical monitoring is needed when using it.     

Efficacy and safety of pemetrexed maintenance chemotherapy for advanced non-small cell lung cancer in a real-world setting

BackgroundPemetrexed maintenance therapy offers a survival benefit in patients with nonprogressive advanced nonsquamous non-small cell lung cancer (NSCLC) with good tolerability. This study was designed to analyze the efficacy and safety of pemetrexed maintenance chemotherapy in advanced nonsquamous NSCLC patients in a real-world setting.MethodsThe response rate (RR) and adverse events in 71 nonsquamous NSCLC patients treated with pemetrexed-based chemotherapy were observed until disease progression or unacceptable toxicities. Measures of survival were analyzed during follow-up.ResultsOf 69 efficacy-evaluable patients, the objective response rate (ORR) was 46.4% and the disease control rate (DCR) was 98.6%. ORR showed no significant difference between patients who received pemetrexed as first-line therapy and those who received pemetrexed as second-line or higher treatment. The median treatment cycle for all patients was 8. The median progression-free survival (PFS) was 9.5 months (m) and median overall survival (OS) was 30.5 m. The univariate and multivariate analyses showed that the number of chemotherapy cycles was an independent factor for PFS. The most common adverse reactions were grade 1 to 2 hematologic toxicities, gastrointestinal reactions, and liver enzyme abnormalities. Only 1 patient experienced a grade 3 gastrointestinal event.ConclusionsPemetrexed maintenance chemotherapy can improve PFS in patients with advanced nonsquamous NSCLC with good tolerability.     

Strategies for maintenance therapy in advanced non-small cell lung cancer: current status, unanswered questions and future directions

Systemic chemotherapy (CT) with platinum-based doublets result in modest improvements in both overall survival (OS) and quality of life in good performance status patients with advanced non-small cell lung cancer (NSCLC). However, although substantial progress has been made in the therapeutic options currently available for these patients, the overall outcome remains poor. Maintenance therapy for patients who achieved at least stable disease after first-line treatment has been an area of intense investigation in recent years as a way of improving outcomes in metastatic NSCLC. Several alternative strategies for prolongation of initial treatment have been evaluated. These include the prolongation of the initial combination CT regimen until disease progression, unacceptable toxicity or a predefined greater number of cycles, continuation with a lower intensity version of the first-line CT regimen or administration of a new active agent immediately after completion of the first-line therapy (switch-maintenance or early second-line therapy). Treatments that have been studied in randomized trials to date include CT, molecularly targeted agents, and immunotherapy approaches. Phase III trials have not revealed a survival benefit for extended first-line CT with combination regimens for more than 4-6 cycles. Nevertheless, early second-line therapy with pemetrexed in nonsquamous tumours and erlotinib have demonstrated to improve OS results, especially in select patient groups characterized by histology and/or molecular profile. This article reviews recent data with maintenance therapy in advanced NSCLC and discusses the implications for routine patient care and future drug development.     

培美曲塞治疗老年晚期非小细胞肺癌疗效分析

目的观察培美曲塞单药二线治疗老年晚期非鳞癌NSCLC的疗效及毒性反应;方法经病理学或细胞学确诊的25例老年晚期NSCLC患者,均接受培美曲塞化疗,培美曲塞以500 mg/m2,第一天静脉滴注,21天为一周期,每例患者至少行2周期化疗;结果 CR 0例,PR 5例,SD 12例,PD 8例,有效率(RR)20.0%,临床获益率(CBR)68.0%。主要不良反应为骨髓抑制和胃肠道反应;结论培美曲塞治疗老年晚期NSCLC具有一定的疗效,毒性反应轻,耐受性好。     

The efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel after cisplatin plus pemetrexed in non-squamous non-small-cell lung cancer patients

BackgroundCarboplatin plus nanoparticle albumin-bound paclitaxel (nab-PTX) is one of the available first-line treatments for non-small cell lung cancer (NSCLC) patients. However, the efficacy of carboplatin plus nab-PTX as second-line, remains unknown. We examined the efficacy of carboplatin plus nab-PTX after cisplatin plus pemetrexed in non-squamous NSCLC patients.MethodsWe retrospectively reviewed advanced non-squamous NSCLC patients who received carboplatin plus nab-PTX as a second-line chemotherapy regimen after cisplatin plus pemetrexed in our hospital between March 2013 and December 2017. We assessed clinical characteristics, efficacy, and toxicities.ResultsForty-four patients were recruited. The overall response rate (ORR) was 29% and the disease control rate (DCR), 69%. The median progression-free survival (mPFS) was 3.7 months (95% CI: 2.4–5.5 months) and the median overall survival, 16.6 months (95% CI:8.8–19.5 months). We assessed the ORR and mPFS using the best overall response in the prior regimen. The ORR and mPFS were better in the PD group (ORR; 44% and mPFS: 5.6 months).ConclusionsCarboplatin plus nab-PTX after cisplatin plus pemetrexed in non-squamous NSCLC patients is a treatment option. There were several cases where cisplatin plus pemetrexed was not effective, but Carboplatin plus nab-PTX was.     

The addition of camrelizumab is effective and safe among unresectable hepatocellular carcinoma patients who progress after drug-eluting bead transarterial chemoembolization plus apatinib therapy

ObjectiveCamrelizumab synergizes with apatinib or transarterial chemoembolization via tumor immunity and chemosensitivity. This study aimed to investigate the efficacy and safety of camrelizumab plus apatinib with or without drug-eluting bead transarterial chemoembolization (DEB-TACE) in unresectable hepatocellular carcinoma (HCC) patients after progression to DEB-TACE plus apatinib.MethodsEighty-nine unresectable HCC patients accepted previous DEB-TACE plus apatinib therapy, then further received second-line camrelizumab plus apatinib with or without DEB-TACE treatment. Treatment responses were calculated at 3 months (M3) and 6 months (M6). Survival and treatment-related adverse events were documented.ResultsObjective response rate and disease control rate were 39.3% and 80.9% at M3; meanwhile, they were 22.4% and 54.1% at M6. Furthermore, the median progression-free survival (PFS) (95% confidence interval (CI)) was 7.0 (6.2-7.8) months with a 1-year PFS rate of 18.4%; the median overall survival (OS) (95% CI) was 17.0 (15.3-18.7) months with a 1-year OS rate of 73.9%. Multivariable Cox's proportional hazards regression analysis presented that 3-4 times (vs. 0 time) of DEB-TACE, apatinib dose duration> 4 months, and camrelizumab dose duration> 5 months independently predicted longer PFS (all P<0.05); meanwhile, declined ECOG PS score, new lesions as progression pattern, 1-2 and 3-4 times (vs. 0 time) of DEB-TACE, apatinib dose duration> 4 months independently predicted prolonged OS (all P<0.05). Moreover, treatment-related adverse events mainly included grade 1-2 fever, gastrointestinal reaction, fatigue, hand-foot skin reaction, and hypertension.ConclusionAfter progression to DEB-TACE plus apatinib treatment, the addition of camrelizumab is effective and safe among unresectable HCC patients.