血清VEGF水平与贝伐珠单抗联合化疗治疗转移性结直肠癌患者疗效的关系研究

目的:研究血清血管内皮生长因子(VEGF)水平与贝伐珠单抗联合化疗治疗转移性结直肠癌患者疗效的关系。方法:选取2015年2月至2016年2月间我院收治的转移性结直肠癌患者80例,按照数字随机表法将患者随机分为观察组(n=40)和对照组(n=40)。对照组给予氟尿嘧啶/奥沙利铂(FOLFOX-6)方案治疗,观察组则在此基础上加用贝伐珠单抗5 mg/kg治疗,d1,两组均进行4个化疗周期,比较两组患者临床疗效及治疗前、治疗后血清VEGF水平,并分析血清VEGF与疗效的相关性。结果:观察组有效率(RR)为52.50%(21/40),高于对照组的30.00%(12/40)(P0.05)。治疗前两组患者血清VEGF水平差异无统计学意义(P0.05),治疗后两组患者血清VEGF水平均较治疗前显著降低,观察组患者血清VEGF水平显著低于对照组患者,观察组VEGF下降幅度显著高于对照组(均P0.05)。经秩相关分析显示,结直肠癌患者治疗后VEGF下降幅度与治疗疗效呈显著正相关(r=0.683,P=0.000)。结论:贝伐珠单抗联合化疗治疗转移性结直肠癌可显著降低患者血清VEGF水平,疗效更佳。     

西妥昔单抗联合FOLFIRI 与单用FOLFIRI 方案治疗转移性结直肠癌近 期疗效的对照研究

目的:比较西妥昔单抗(爱必妥)联合FOLFIRI化疗方案与单用FOLFIRI化疗方案治疗转移性结直肠癌患者的临床疗效和毒副反应。方法:回顾性分析2008年1月至2011年11月解放军总医院经组织病理学证实的46例转移性结直肠癌患者临床资料,其中西妥昔单抗联合FOLFIRI化疗方案组22例,单用FOLFIRI方案组24例,观察比较两组方案的近期疗效和不良反应。结果:两组方案治疗转移性结直肠癌的客观缓解率(CR+PR)分别为41.6%和12.5%,其中联合治疗方案治疗效果明显优于单用FOLFIRI化疗方案,两组比较差异有统计学意义(P<0.05)。患者出现的不良反应有痤疮样皮疹、腹泻、骨髓抑制、恶心呕吐、脱发等。除痤疮样皮疹和腹泻外,两组患者毒副反应无显著性差异。结论:西妥昔单抗联合FOLFIRI化疗方案治疗K-Ras基因野生型转移性结直肠癌近期疗效显著,毒副反应较单用FOLFIRI方案无明显增加,患者可以耐受。     

贝伐珠单抗联合化疗二线及以上治疗晚期非鳞型非小细胞肺癌的临床观察

目的：考察贝伐珠单抗联合化疗二线及以上治疗晚期非鳞型非小细胞肺癌的疗效和安全性。方法：28 例经病理组织学或细胞学证实的晚期非鳞型非小细胞肺癌患者接受贝伐珠单抗联合化疗的二线及以上治疗,其间,贝伐珠单抗所用剂量为7.5 mg ? kg -1,在化疗第1 d 静滴给予;化疗方案包括培美曲塞加或不加铂类、白蛋白结合型紫杉醇加或不加铂类及替吉奥以及吉西他滨/ 紫杉醇/ 多西紫杉醇加或不加铂类。各治疗方案每3 周为1 个周期,持续4 个周期,然后维持治疗,直至受试者不能耐受或疾病进展。按RECIST 1.1 版评价疗效,按NCI-CTC 4.0版评价不良反应。结果：28 例受试者中,无完全缓解病例,部分缓解11 例(39.3％ ),稳定16 例（57.1％ ),进展1 例(3.6％ );客观缓解率为39.3％ (11/28),疾病控制率为96.4％ (27/28);中位无进展生存期为5 个月,中位总生存期为10 个月。亚组数据分析可见,贝伐珠单抗联合化疗各方案亚组中,培美曲塞方案受试者的中位无进展生存期为6 个月,疗效最好,较其他各方案亚组有统计学差异（P=0.028）。安全性数据分析显示,与贝伐珠单抗相关的主要不良反应有Ⅰ ~ Ⅲ度高血压以及Ⅰ / Ⅱ度蛋白尿/ 出血/ 发热。结论：贝伐珠单抗联合化疗用于二线及以上治疗晚期非鳞型非小细胞肺癌的疗效较单纯化疗有一定改善,且毒副反应可耐受,对经济上可以接受的患者值得推荐使用。     

FOLFOX方案联合西妥昔单抗治疗转移性结直肠癌的近期疗效及安全性分析

目的：探讨FOLFOX方案联合西妥昔单抗治疗转移性结直肠癌的近期临床疗效及安全性。方法：选择2009年2月～2011年2月本院诊治的42例转移性结直肠癌患者为研究对象,采用随机数字表法将其随机分入对照组与观察组,其中对照组20例,观察组22例。对照组患者接受FOLFOX方案治疗,每2周重复1次,治疗3周期;观察组患者给予FOLFOX方案联合西妥昔单抗治疗。比较两组的近期疗效及毒副反应。结果：观察组的客观缓解率和疾病控制率均显著高于对照组,差别具有统计学意义（P〈0．05）;骨髓抑制、消化道反应、神经毒性是两组常见的毒副反应,两组患者骨髓抑制、消化道反应、神经毒性、脱发及肝功能损害发生率无显著差别（P〉0．05）,观察组痤疮样皮疹的发生率显著高于对照组（36．4％VS0,P〈0．05）。结论：西妥昔单抗联合FOLFOX方案可提高转移性结直肠癌患者的近期疗效,毒副反应可耐受。     

转移性结直肠癌抗血管生成靶向治疗的研究进展

近年来,由于各种新的化疗药物及分子靶向药物的使用,转移性结直肠癌(metastatic colorectal cancer,m CRC)的个体化治疗逐步取得了重要的成果。研究表明,抗血管生成靶向药物与化疗药物的联合使用作为转移性结直肠癌的一线治疗方案,可明显改善治疗效果,延长患者的生存时间。血管内皮生长因子(vascularendothelial growth factor,VEGF)是肿瘤血管生成过程中最主要的因子。贝伐单抗是通过基因工程技术得到的针对血管内皮生长因子-A(VEGF-A)的单克隆抗体,作为抗血管生成靶向药物用于转移性结直肠癌的临床治疗。本文对近年来转移性结直肠癌的抗血管生成靶向治疗,尤其是贝伐单抗治疗的相关研究进展进行综述并展望未来抗血管生成靶向治疗的发展前景。     

西妥昔单抗和贝伐珠单抗治疗晚期结直肠癌的有效性和安全性比较

目的:比较西妥昔单抗和贝伐珠单抗治疗晚期结直肠癌的有效性和安全性。方法:选取2014年1月～2017年8月我院收治的晚期结直肠癌患者100例,根据患者入院先后顺序随机分为两组,所有患者均给予FOLFIRI方案进行化疗,A组在化疗的基础上给予贝伐珠单抗进行治疗,B组在化疗的基础上给予西妥昔单抗进行治疗。比较两组患者临床治疗的缓解率、控制率及不良反应的发生情况,对所有患者随访1年,记录并比较两组患者的无进展生存期。结果:两组患者的缓解率、控制率、恶心呕吐、头晕、延迟性腹泻、肝肾损伤、白细胞减少、血小板减少和尿蛋白的发生率相比均无统计学差异(P0.05),但B组患者骨髓抑制和皮疹的发生率显著高于A组(P0.05);两组患者的无进展生存期相比无统计学差异(P0.05)。结论:西妥昔单抗和贝伐珠单抗治疗晚期结直肠癌的临床效果相当,且不良反应较轻,以Ⅰ～Ⅱ度为主,患者均可耐受,对症治疗后均有所缓解。西妥昔单抗易引发骨髓抑制和皮疹,在临床应用过程中需注意并进行有效预防和积极处理。     

贝伐珠单抗联合化疗治疗晚期非鳞非小细胞肺癌的临床观察

目的:观察贝伐珠单抗联合化疗对晚期非小细胞肺癌患者的疗效、安全性及影像学改变。方法:对2007年至2014年于我院治疗的晚期NSNSCLC(非鳞非小细胞肺癌non-squamous non-small cell lung cancer)患者,给予贝伐珠单抗(15 mg/kg或7.5mg/kg)联合化疗(紫杉醇175 mg/m~2,d1,卡铂AUC=5或6,d1,q3 w)6周期及贝伐珠单抗维持治疗(15 mg/kg或7.5 mg/kg,d1,q3w)。观察疗效、不良反应、肺部病灶空洞改变的情况、恶性胸腔积液的治疗效果及部分患者EGFR、KRAS基因突变状况。结果:共观察26例患者,均接受贝伐珠单抗联合化疗,17例行贝伐珠单抗维持治疗。部分缓解(partial response,PR)、疾病稳定(stable disease,SD)、疾病进展(disease progression,PD)率分别为53.8%、42.3%、3.8%。中位无进展生存期(progression free survival,PFS)为11.0个月,中位总生存期(overall survival,OS)达25.8个月。26例患者中15.4%治疗后病变发生空洞改变,空洞组的2年、3年生存率略高于无空洞组,但无统计学差异(P值分别为0.586、0.509)。13例患者伴有恶性胸腔积液,胸腔积液的疾病控制率为100%。11例患者标本可进行EGFR基因检测,敏感突变占36.4%,未突变占63.6%。对10例患者标本行KRAS基因检测,均为突变阴性。不良反应包括骨髓抑制、消化道反应、鼻衄、咯血、高血压、蛋白尿等。大多数不良反应程度较轻,可控制。结论:贝伐珠单抗联合化疗治疗晚期NSNSCLC患者疗效确切,副反应可耐受,控制恶性胸腔积液效果较好。肺部病灶空洞改变的临床意义有待进一步研究。     

贝伐珠单抗联合化疗治疗晚期结直肠癌的临床疗效

目的:探讨晚期结直肠癌采用贝伐珠单抗联合化疗的临床疗效,为临床治疗提供参考。方法:按照随机数字表法将2010年2月~2013年2月我院收治的50例晚期结直肠癌患者分为两组,观察组采用贝伐珠单抗联合奥沙利铂,卡培他滨化疗,对照组单用奥沙利铂,卡培他滨进行化疗,比较两组的临床疗效、血清肿瘤标志物浓度变化及不良反应。结果:化疗4个周期后观察组有效率为56.00%高于对照组的24.00%,差异有统计学意义(P0.01),观察组疾病控制率为84.00%高于对照组的60.00%,差异有统计学意义(P0.05);观察组治疗后的CEA、CA242、CA19-9浓度均低于对照组,差异有统计学意义(P0.01);化疗后两组不良反应主要有恶心、呕吐、食欲减低等胃肠道反应,乏力,肝功能损害,骨髓抑制,脱发,贫血以及中性粒细胞下降等,其中观察组乏力,肝功能损害发生率低于对照组,差异有统计学意义(P0.05),其余不良反应两组差异无统计学意义(P0.05)。结论:结直肠癌采用贝伐珠单抗联合化疗治疗具有近期疗效好,安全性高等特点,临床有重要参考价值。     

重组人血管内皮抑素联合FOLFIRI方案治疗结直肠癌肝转移的临床观察

目的:探讨重组人血管内皮抑素(恩度)联合FOLFIRI方案治疗结直肠癌肝转移的临床疗效与安全性。方法:选取结直肠癌肝转移患者58例,随机分为观察组与对照组,每组各29例。对照组予以FOLFIRI方案,观察组予以恩度联合FOLFIRI方案治疗,均于治疗4个周期后,观察和比较临床疗效及毒副反应的发生情况,并随访患者的生存情况。结果:观察组与对照组的临床总有效率(RR)分别为44.83%和24.14%,疾病控制率(DCR)分别为89.66%和65.52%,差异具有统计学意义(P0.05);毒副反应的发生率分别为44.83%和37.93%,差异无统计学意义(P0.05)。观察组与对照组无进展生存期(PFS)分别为7.5个月和4.3个月,总生存期(OS)分别为13.2个月和6.9个月,差异均具有统计学意义(P0.05)。结论:重组人血管内皮抑素联合FOLFIRI方案治疗结直肠癌肝转移的临床疗效较单用FOLFIRI方案更好,但并未显著增加毒副反应,安全性较好,值得临床推广应用。     

贝伐珠单抗在肿瘤治疗中的应用研究进展

贝伐珠单抗是一种重组人源化免疫球蛋白 G1 单克隆抗体,可通过抑制血管内皮生长因子活性及抗血管生成,达到抑制肿瘤生长 的目的,目前已广泛用于结直肠癌、肺癌、卵巢癌等多种肿瘤的治疗,尤其是通过与基础化疗结合,能显著提高治疗的有效率以及延长 肿瘤患者的无进展生存期和总生存期。综述贝伐珠单抗的抗肿瘤作用机制、在不同肿瘤治疗中的应用、用于肿瘤治疗时机与疗效差异以 及不良反应和防治。     

草酸铂联合FL三周方案二线治疗晚期肠癌25例疗效分析

目的评价草酸铂（L-OHP）联合氟脲嘧啶（5-FU）、甲酰四氢叶酸钙（CF）二线治疗晚期复发大肠癌的疗效和不良反应。方法L-OHP 130 mg/m^2,静脉滴入,2 h,d1;CF 100 mg/m^2,5-FU前2小时静脉滴入,d1-d5;5-FU 500 mg/m^2,静脉滴入,6-8 h,d1-d5,21 d为1个周期。结果全组CR 1例,PR 3例,SD 17例,PD 4例,总有效率为16%,疾病控制率为84%。主要不良反应为中性粒细胞减少、消化道反应及外周神经毒性。结论L-OHP联合5-FU、CF方案（OFL）二线治疗晚期复发大肠癌安全、有效,毒性反应可耐受。     

Dynamic monitoring the TCR CDR3 spectratypes in patients with metastatic CRC treated with a combination of bevacizumab, irinotecan, fluorouracil, and leucovorin

In the present study, either modified IFL regimen (modified irinotecan, fluorouracil and leucovorin, mIFL) alone or in combination with bevacizumab was used to treat patients with metastatic colorectal cancer (CRC). Treatment efficacy was assessed using coupled tomography imaging diagnosis. The toxicity accompany with treatment was evaluated, as well as T cell receptor (TCR) repertoire before and several cycles after therapy was dynamically monitored by analyzing the complementarity-determining region 3 (CDR3) length distribution within CD4⁺ and CD8⁺ T cell subsets. The degrees of normalization of the T cell repertoire in CRC patients treated with the two methods were compared. The results showed that mIFL combined with bevacizumab was more effective in treating patients with metastatic CRC, and was accompanied by an increase in side effects such as proteinuria and hematuria. An even more restricted CDR3 profile in patients with metastatic CRC compared with healthy control has been detected. A prominent usage of TCR β chain variable (BV) gene BV12 and BV16 families within the CD4⁺ T cell subset and BV19 and BV21 families within the CD8⁺ T cell subset have been found before treatment. Moreover, CD8⁺ T cells showed more restricted patterns than CD4⁺ T cells, especially in patients before treatment. For patients with stable disease (SD) or partial remission (PR) after treatment, a less restricted CDR3 profile in post-treatment compared with pre-treatment has been found, but the opposite result was observed for patients with progressive disease (PD). The less restricted CDR3 pattern suggested a trend toward normalization of the TCR repertoire. The normalization of TCR repertoire significantly increased in patients treated with mIFL in combination with bevacizumab, but slightly in patients treated with mIFL alone. The results demonstrate a positive correlation between post-therapy TCR repertoire normalization and remission of metastatic CRC.     

紫杉醇在治疗晚期或复发性宫颈癌中的应用分析

为了探讨紫杉醇在治疗晚期或复发性宫颈癌中的疗效和安全性,为不适合手术或者放射治疗的患者(包括晚期或复发性宫颈癌患者)注射紫杉醇170 mg/m^2、卡铂5 mg·mL^-1·min^-1、贝伐珠单抗12 mg/kg治疗,每20 d一次,并记录期间的不良反应,直至疾病有所缓解或其毒性有所限制。总共有38名患者接受了平均8个治疗周期(范围2~25),中期随访值为18.5个月(范围2~29)。结果显示,19名患者(50.0%)经历完全反应,而15名患者经历(39.4%)部分反应,平均持续时间为6个月。3级和4级血液学毒性表现为中性粒细胞减少症15例(39.4%)、白细胞减少症13例(34.2%)、贫血症13例(34.2%)、血小板减少症11例(28.9%)。1名接受过骨盆照射的患者发生了2级直肠阴道瘘。本研究表明,紫杉醇、卡铂和贝伐单抗的组合对于晚期或复发性宫颈癌患者是有效且安全的。     

西妥昔单抗联合FOLFIRI 方案治疗晚期胃癌的疗效观察

目的:观察西妥昔单抗联合FOLFIRI方案用于一线治疗失败的局部晚期或转移性胃癌患者,观察其疗效和不良反应,并观察其与疗效和预后的相关性。方法:每2疗程评价肿瘤病灶情况,观察不良反应,随访肿瘤进展情况及生存期。按照实体瘤疗效评价标准(Response Evaluatione Criteria in solid Tumors,RECIST)进行肿瘤缓解评估,按照国立癌症研究所常见不良事件评价标准3.0版(NCI一CTCAE3.0)进行不良事件分级。计算肿瘤缓解率、中位至疾病进展时间和中位总生存期。结果:在38例至少完成了2个周期治疗并进行了疗效评价的患者中,观察到1例完全缓解(CR),占0.03%;13例部分缓解(PR),占34.00%;总的缓解率(ORR=CR+PR)为37.00%。疾病稳定(SD)的患者有20例,占53.00%;疾病控制率(Disease Control Rate,DCR=CR+PR+SD)为89.00%;疾病进展(PD)的患者为4例,占11.00%。本研究方案总体安全性良好,未发生一例治疗相关性死亡。其中III/IV度粒细胞减少的发生率为52.5%,粒缺性发热的发生率为13.1%,III/IV度度贫血的发生率为29.5%,III/IV度度血小板下降的发生率为8.2%。III/IV度非血液学毒性包括恶心(8.2%),呕吐(6.6%),口腔炎(1.6%),腹泻(6.6%),感染(4.9%),乏力(4.9%),肠梗阻(6.6%),转氨酶升高(l.6%),过敏反应(l.6%)和皮疹(9.8%)。结论:本研究显示在晚期胃癌患者的二线治疗中西妥昔单抗联合FOLFIRI是一个安全有效的方案,需要进一步的研究寻找有效的生物标记物。     

Colorectal cancer metastatic disease progression in Australia: A population-based analysis

BackgroundNo previous Australian population-based studies have described or quantified the progression of colorectal cancer (CRC) to metastatic disease. We describe patterns of progression to metastatic disease for an Australian cohort diagnosed with localised or regional CRC.MethodsAll localised and regional CRC cases in the New South Wales Cancer Registry diagnosed during 2000–2007 were followed to December 2011 for subsequent metastases (identified by subsequent disease episode notifications) or CRC death. Cox regression was used to identify factors associated with metastatic progression.ResultsAfter a median 5.3 years follow-up, 26.4% of the 12757 cases initially diagnosed with localised or regional colon cancer had developed metastatic disease, as had 29.5% of the 7154 rectal cancer cases. For both cancer sites, risk of metastatic progression was significantly higher for those initially diagnosed with regional disease (adjusted hazard ratio [aHR] 3.49 for colon, 2.66 for rectal cancer), and for older cases (e.g. aHR for >79 years vs <60 years: 1.38 for colon, 1.69 for rectal cancer). Risk of disease progression was significantly lower for females, and varied by histology type. For colon cancer, the risk of disease progression decreased over time. For rectal cancer, risk of metastatic progression was significantly higher for those living in more socioeconomically disadvantaged areas compared with those in the least disadvantaged area.ConclusionsAn understanding of the variation in risk of metastatic progression is useful for planning health service requirements, and can help inform decisions about treatment and follow-up for colorectal cancer patients.     

Symptom burden & quality of life among patients receiving second-line treatment of metastatic colorectal cancer: a retrospective review

ABSTRACT: BACKGROUND: Bevacizumab (B) and cetuximab (C) are both approved for use in the treatment of metastatic colorectal cancer (mCRC) in the second-line. We examined self-reported symptom burden during second-line treatment of mCRC. METHODS: Adult mCRC patients treated in the second-line setting with a regimen that included B, C, or chemotherapy only (O) and who had completed [greater than or equal to] 1 Patient Care Monitor (PCM) surveys as part of routine clinical care were drawn from the ACORN Data Warehouse. Primary endpoints were rash, dry skin, itching, nail changes, nausea, vomiting, fatigue, burning in hands/feet, and diarrhea. Linear mixed models examined change in PCM scores across B, C and O (B=reference). RESULTS: 182 patients were enrolled (B: n = 106, C: n = 38, O: n = 38). Patients were 51% female, 67% Caucasian, with mean age of 62.0 (SD=12.6). Groups did not differ on demographic or clinical characteristics. The most common second-line regimens were FOLFIRI +/- B or C (23.1%) and FOLFOX +/- B or C (22.5%). Results showed baseline scores to be strongly predictive of second-line symptoms across all PCM items (all p < .0001 except for Rash, p = .0013). Controlling for baseline, patients on B tended to have more stable and less severe symptoms. Patients on C had more severe rash, dry skin, and itching and had nail change scores that worsened faster than did B patients. CONCLUSIONS: Patients receiving second-line treatment for mCRC with B report less symptom burden, especially dermatologic, compared to patients treated with C.