贝伐珠单抗在结直肠癌治疗中的应用

近年来,随着对肿瘤生物学认识的深入,以贝伐珠单抗、西妥昔单抗为代表的分子靶向治疗药物正逐渐丰富着晚期结直肠癌的治疗选择.贝伐珠单抗是一种人源化、人鼠嵌合抗血管内皮生长因子的单克隆抗体,是第一个被美国FDA批准用于治疗晚期结直肠癌患者的抗血管生成药物,以贝伐珠单抗为基础进行的临床研究也证实了它能改善晚期结直肠癌患者的生存期.全文通过回顾近年来发布的结直肠癌治疗领域有关贝伐珠单抗的临床研究,对其在晚期结直肠癌一线、二线和维持治疗以及在结直肠癌术后辅助治疗领域中的应用做一系统综述.     

贝伐珠单抗联合奥沙利铂+卡培他滨化疗治疗转移性结直肠癌的疗效及安全性

目的 探讨贝伐珠单抗联合奥沙利铂+卡培他滨化疗治疗转移性结直肠癌的疗效及安全性.方法 采用随机数字表法将78例转移性结直肠癌患者分为对照组和研究组,每组39例,对照组患者给予奥沙利铂+卡培他滨化疗,研究组患者给予贝伐珠单抗联合奥沙利铂+卡培他滨治疗.治疗2个疗程后,比较两组患者的临床疗效、肿瘤标志物[癌胚抗原(CEA)...     

卡培他滨节拍化疗在转移性结直肠癌维持治疗中的探索性Ⅱ期研究

背景与目的：转移性结直肠癌患者一线诱导化疗后的维持治疗方案如何选择，尚存在争议。本研究将卡培他滨节拍化疗应用于转移性结直肠癌维持治疗，评估其疗效与安全性。方法：本研究是单臂、单中心探索性研究。接受一线诱导化疗（XELOX、mFOLFOX6、FOLFIRI）18~24周的转移性结直肠癌患者，评估为临床获益后接受卡培他滨500 mg，每天2次口服维持治疗，直至疾病进展。研究首要终点是无进展生存期（progression-free survival，PFS），包括卡培他滨维持治疗的PFS和诱导化疗续贯维持治疗的PFS。次要终点为总生存期（overall survival，OS）和不良反应。结果：2014年10月16日—2017年12月31日于上海交通大学医学院附属瑞金医院接受治疗的转移性结直肠癌患者37例接受节拍化疗维持治疗。中位随访时间15.0个月（4.0~41.4个月）。节拍化疗维持治疗的中位PFS为5.6个月（1.7~38.5个月），诱导化疗续贯维持治疗的中位PFS为11.4个月（6.8~44.3个月）。主要的不良反应为白细胞减少（8/37，21.6%）、恶心呕吐（5/37，13.5%）和手足综合征（3/37，8.1%）。没有1例患者出现3~4级严重不良反应。结论：卡培他滨节拍化疗应用于转移性结直肠癌诱导化疗后维持治疗安全、有效。     

卡培他滨和雷替曲塞分别联合贝伐珠单抗治疗晚期结直肠癌的疗效及安全性比较

目的:探讨卡培他滨和雷替曲塞分别联合贝伐珠单抗对晚期结直肠癌患者疗效及安全性的影响。方法:回顾性分析我院2014年1月至2018年12月收治的晚期结直肠癌患者共147例临床资料,其中采用卡培他滨联合贝伐珠单抗治疗77例设为对照组,采用雷替曲塞联合贝伐珠单抗治疗70例设为观察组;比较两组近期疗效、随访生存情况及不良反应发生情况。结果:两组ORR和DCR比较差异无显著性（P＞0.05）;两组中位PFS和OS比较差异无显著性（P＞0.05）;观察组I-II级恶心呕吐、周围神经毒性及手足综合征发生率均显著低于对照组（P＜0.05）;同时观察组III-IV级手足综合征发生率显著低于对照组（P＜0.05）。结论:相较于卡培他滨,雷替曲塞联合贝伐珠单抗治疗晚期结直肠癌可获得相近疾病控制和生存获益,同时还有助于减轻药物不良反应,提高治疗耐受性。     

贝伐单抗在转移性结直肠癌治疗中的应用

进入二十一世纪,靶向药物问世使许多晚期肿瘤化疗效果显著提高,其中针对血管内皮生长因子(VEGF)的人源化单克隆抗体一贝伐单抗(bevaci-zumab,Avastin),在晚期或转移性结直肠癌一线或二线治疗中均有明显效果,延长生存,且不良反应大多为轻到中度,重度不良反应较少.     

卡培他滨节拍化疗在晚期结直肠癌维持治疗中的疗效观察

摘 要：［目的］ 探讨卡培他滨节拍化疗维持治疗晚期结直肠癌的疗效及安全性。［方法］ 入组69例复发转移性结直肠癌患者,完成联合化疗后疗效评价无疾病进展,根据治疗方法不同分为节拍化疗组、常规化疗组。节拍化疗组32例给予小剂量卡培他滨节拍化疗500mg,2次/d,持续口服,28d为1个周期;常规化疗组37例每次给予卡培他滨 1250mg/m2,2次/d,连续14d,休7d,21d为1个周期;4个周期后观察毒副反应及近期疗效,Kaplan-Meier法绘制中位无进展生存期（PFS）生存曲线图。［结果］ 节拍化疗组与常规化疗组有效率分别为15.63%和16.22%（χ2=0.004,P=0.947）,疾病控制率分别为71.88%和70.27%（χ2=0.021,P=0.884）,差异均无统计学意义。节拍化疗组中位PFS为8.6个月,常规化疗组为7.9个月,差异无统计学意义(χ2=0.367,P=0.554)。节拍化疗组不良反应发生率均低于常规化疗组,且骨髓抑制及手足综合征发生率两组比较差异有统计学意义(P<0.05)。［结论］卡培他滨节拍化疗较常规化疗在结直肠癌晚期维持治疗中显示出等效低毒的特点,值得临床进一步推广。     

贝伐珠单抗联合化疗治疗晚期结直肠癌的临床观察

目的:观察贝伐珠单抗联合化疗治疗晚期结直肠癌(ACRC)的疗效。方法:回顾性分析西安交通大学第一附属医院2010年10月到2012年4月收治的28例ACRC患者应用贝伐珠单抗联合化疗的疗效、生存期及不良反应。结果:完全缓解(CR)1例,部分缓解(PR)12例,稳定(SD)8例,进展(PD)7例。有效率(RR)为46.43%(13/28),疾病控制率(DCR)为75%(21/28)。生存期为3-16个月,中位生存期(MST)为14.7月。与贝伐珠单抗相关的不良反应为蛋白尿4例,皮疹4例,高血压2例,便血2例。未发现血栓栓塞、胃肠穿孔、充血性心力衰竭等严重不良反应。结论:贝伐珠单抗与化疗联合治疗ACRC可增强疗效,有延长生存期的趋势,不良反应轻,耐受性好。     

卡培他滨联合草酸铂治疗晚期结直肠癌36例的临床研究

目的：研究卡培他滨联合草酸铂治疗晚期结直肠癌的近期疗效和毒副反应。方法：希罗达1250mg／m^2，每日2次口服．第1天～14天：草酸铂(奥沙利铂)130mg／m^2溶入5％葡萄糖注射液250mL中静脉滴注2h，第1天，21天为1周期。至少连用2个周期后评价疗效。结果：37例患者CR3例(8．1％)、PR16例(43．2％)、SD13例(35．1％)、PD5例(13．5％)，有效率51．4％。主要毒副反应为恶心、呕吐、腹泻、血白细胞减少、手足综合征、末梢神经异常、口腔黏膜炎。结论：卡培他滨联合草酸铂化疗晚期结直肠癌的疗效确切，并可提高患者的生活质量，毒副反应小，患者可以耐受。     

贝伐单抗治疗转移性结直肠癌研究进展

贝伐单抗(bevacizumab)是一种重组人源化抗血管内皮生长因子的单克隆抗体,可与肿瘤细胞上的血管内皮生长因子(VEGF)特异性结合,通过抑制血管生成而抑制肿瘤生长.贝伐单抗已于2004年2月获FDA批准,与5-氟尿嘧啶为基础的化疗方案联合一线治疗转移性结直肠癌.推荐剂量为5 mg/kg,每14天给药1次,静脉滴注.贝伐单抗的耐受性良好,较常见的不良反应有高血压、出血和血栓形成.     

卡培他滨治疗转移性结直肠癌的初步疗效观察

结直肠癌在欧洲癌症死因的第二位[1],在我国正呈逐渐上升的趋势.转移性结直肠癌的治疗较为困难,平均生存期6～9个月[2],5年以上生存不到5%.     

Cost-effectiveness of capecitabine and bevacizumab maintenance treatment after first-line induction treatment in metastatic colorectal cancer

AimCapecitabine and bevacizumab (CAP-B) maintenance therapy has shown to be more effective compared with observation in metastatic colorectal cancer patients achieving stable disease or better after six cycles of first-line capecitabine, oxaliplatin, bevacizumab treatment in terms of progression-free survival. We evaluated the cost-effectiveness of CAP-B maintenance treatment.MethodsDecision analysis with Markov modelling to evaluate the cost-effectiveness of CAP-B maintenance compared with observation was performed based on CAIRO3 study results (n = 558). An additional analysis was performed in patients with complete or partial response. The primary outcomes were the incremental cost-effectiveness ratio (ICER) defined as the additional cost per life year (LY) and quality-adjusted life years (QALY) gained, calculated from EQ-5D questionnaires and literature and LYs gained. Univariable sensitivity analysis was performed to assess the influence of input parameters on the ICER, and a probabilistic sensitivity analysis represents uncertainty in model parameters.ResultsCAP-B maintenance compared with observation resulted in 0.21 QALYs (0.18LYs) gained at a mean cost increase of €36,845, yielding an ICER of €175,452 per QALY (€204,694 per LY). Varying the difference in health-related quality of life between CAP-B maintenance and observation influenced the ICER most. For patients achieving complete or partial response on capecitabine, oxaliplatin, bevacizumab induction treatment, an ICER of €149,300 per QALY was calculated.ConclusionCAP-B maintenance results in improved health outcomes measured in QALYs and LYs compared with observation, but also in a relevant increase in costs. Despite the fact that there is no consensus on cost-effectiveness thresholds in cancer treatment, CAP-B maintenance may not be considered cost-effective.     

参一胶囊联合卡培他滨维持治疗晚期大肠癌的临床研究

目的评价参一胶囊联合卡培他滨维持治疗晚期大肠癌的疗效和安全性。方法对61例经过一线治疗后达到完全缓解、部分缓解或稳定的晚期大肠癌患者,采用随机分组的方法进行维持治疗。其中试验组（30例）应用参一胶囊联合卡培他滨维持治疗,对照组（31例）单用卡培他滨维持治疗。结果试验组和对照组的中位无进展生存期（PFS）分别为10.0个月和8.0个月,试验组无疾病进展生存状况显著优于对照组（P=0.003）。试验组骨髓抑制发生率显著低于对照组（P〈0.05）。结论对于晚期大肠癌患者,参一胶囊联合卡培他滨维持治疗对比单用卡培他滨维持治疗能延长患者的PFS,减少骨髓抑制的发生。     

羟基喜树碱联合卡培他滨治疗FOLFOX化疗失败晚期大肠癌的临床观察

目的观察羟基喜树碱（HCPT）联合卡培他滨（Cap）治疗FOLFOX化疗失败后晚期大肠癌的近期疗效及毒性反应。方法36例FOLFOX治疗失败的晚期大肠癌患者采用HCPT6mg／m^2,静脉滴注,d1～5;卡培他滨1000mg／m^2,口服,2次／d,第1～14天,3周为一周期,至少2周期后评价疗效。按WHO标准评价近期疗效和毒副反应。结果可评价疗效者36例,CR1例,PR12例,有效率为36．1％。中位至疾病进展时间（mTFP）6．7个月,中位生存时间（MST）15．8个月,1年生存率41．7％。毒副反应主要是骨髓抑制、手足综合征、胃肠道反应,全组无治疗相关性死亡。结论羟基喜树碱联合卡培他滨治疗FOLFOX失败晚期大肠癌有较好的疗效,毒副反应可以耐受,值得进一步观察。     

A phase II study of oxaliplatin, dose-intense capecitabine, and high-dose bevacizumab in the treatment of metastatic colorectal cancer

Background

This study was designed to determine the efficacy and tolerability of a novel 2-week regimen of capecitabine, oxaliplatin (OHP), and bevacizumab in patients with chemo-naive advanced colorectal cancer.

Patients and Methods

Nineteen patients with previously untreated advanced colorectal cancer received capecitabine at 1000 mg/m² twice a day on days 1-5 and days 8-12 of a 14-day cycle, and OHP at 85 mg/m² and bevacizumab at 10 mg/kg every 2 weeks. Because of unacceptable toxicities, the capecitabine dose was reduced to 850 mg/m². Thirty-one additional patients were treated at the lower capecitabine dose. Treatment continued until disease progression, persistent intolerable toxicity, or physician and/or patient discretion.

Results

Overall, toxicities were better managed and tolerated at the 850 mg/-m² capecitabine dose. The most common treatment-related grade ≥ 3 toxicities were diarrhea and sensory neuropathy. In the first 19 subjects, the response rate was 63% (95% confidence interval [CI], 38%-84%) and 5 patients had stable disease; median progression-free survival (PFS) was 10.1 months (95% CI, 5.7-19.5 months). In the subsequent 31 patients, the response was 42% (95% CI, 25%-61%); 11 patients had stable disease and median PFS was 10.4 months (95% CI, 6.9-15.4); median overall survival was 24.8 months (95% CI, 12.9-39.7).

Conclusions

This novel regimen of capecitabine at 850 mg/m² twice a day on days 1-5 and days 8-12 and OHP at 85 mg/m²and bevacizumab at 10 mg/kg every 14 days is clinically active in advanced colorectal cancer. The toxicity profile of this regimen is consistent with the standard every-3-week dosing schedule.     

A randomized study of KRAS-guided maintenance therapy with bevacizumab,erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial

BackgroundMaintenance treatment (mt) with bevacizumab (bev) ± erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev ± erlo and low-dose capecitabine (cap).Patients and methodsIncluded patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0–1 and no major comorbidities. Treatment with XELOX/FOLFOX or XELIRI/FOLFIRI + bev was given for 18 weeks. After induction, patients without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev ± erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression-free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed.ResultsWe included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization. PFSr was 64.7% versus 63.6% in wt-B versus wt-BE, P = 1.000; and 75% versus 66.7% in mut-B versus mut-C, P = 0.579, with no significant difference in median PFS and overall survival (OS). In the pooled cohort, median PFS was 3.7 months in wt-B (N = 64) and 5.7 months in wt-BE (N = 62) (hazard ratios 1.03, 95% confidence interval 0.70–1.50, P = 0.867). The frequency of any grade 3/4 toxicities during mt was: 28%/58%/18%/15% (wt-B/wt-BE/mut-B/mut-C).ConclusionsAddition of erlo to bev as mt in KRAS wt mCRC did not significantly improve PFS or OS, but it did increase toxicity. KRAS status does not seem to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results.ClinicalTrials.govNCT01229813.     

阿帕替尼联合消岩汤治疗晚期非鳞非小细胞肺癌临床疗效观察

  目的  研究观察甲磺酸阿帕替尼片联合消岩汤治疗晚期非鳞非小细胞肺癌（non-small cell lung cancer,NSCLC）的临床疗效。  方法  选取晚期非鳞NSCLC患者38例,随机分为阿帕替尼治疗组18例（A组）,阿帕替尼联合消岩汤加减方治疗组20例（B组）,二组治疗期间均未行手术及放、化疗。  结果  晚期非鳞NSCLC患者服用阿帕替尼后中位无进展生存期（median progression free survival,mPFS）可达3个月,阿帕替尼联合消岩汤组mPFS、客观缓解率（objective response rate,ORR）及疾病控制率（disease control rate,DCR）较阿帕替尼单药组差异无统计学意义（P>0.05）;在改善临床症状及不良反应方面,阿帕替尼联合消岩汤组均优于阿帕替尼单药组（P < 0.05）。  结论  阿帕替尼联合消岩汤加减方治疗晚期非鳞NSCLC可改善患者临床症状,并降低不良反应的发生率。