伊立替康联合雷替曲塞或5-FU二线治疗晚期结直肠癌的疗效比较

目的 比较伊立替康联合雷替曲塞方案与伊立替康联合5-FU方案二线治疗晚期结直肠癌的临床疗效。方法 选取经一线化疗失败行二线治疗的60例晚期结直肠癌患者,根据不同二线治疗方案,将其分为观察组和对照组,每组30例。观察组采用伊立替康联合雷替曲塞方案治疗,对照组采用伊立替康联合5-FU方案（FOLFIRI方案）,治疗结束后比较两组患者的近期疗效及不良反应,并观察总生存期（OS）和疾病进展时间（TTP）。结果 观察组和对照组患者的总有效率比较差异无统计学意义（26.67% vs 13.33%,χ²=1.67,P=0.20）;观察组患者疾病控制率高于对照组,差异有统计学意义（63.33% vs 36.67%,χ²=4.27,P=0.04）;观察组中位OS和中位TTP较对照组长,两组比较差异均有统计学意义（9.9个月 vs 7.5个月,χ²=4.461,P=0.012;5.0个月 vs  3.7个月,χ²=6.735,P=0.022）;观察组骨髓抑制、胃肠道不良反应等发生率与对照组比较差异无统计学意义（P＞0.05）。结论 伊立替康联合雷替曲塞二线治疗晚期结直肠癌疗效肯定,较FOLFIRI方案可延长生存期,不良反应更轻,可作为一线化疗失败患者的可选治疗方案。     

周剂量伊立替康联合雷替曲塞在晚期大肠癌二线治疗中的效果及安全性分析

目的探讨周剂量伊立替康联合雷替曲塞二线治疗晚期大肠癌的疗效及安全性。方法选取2014年3月至2016年9月间张家港澳洋医院三兴分院收治的66例晚期结直肠腺癌患者,均经过奥沙利铂与氟尿嘧啶(5-FU)(FOLFOX方案)一线治疗。按照入院先后顺利分为观察组和对照组,每组33例,观察组患者采用周剂量伊立替康联合雷替曲塞作为二线治疗方案,对照组患者采用伊立替康、5-FU和亚叶酸钙(FOLFIRI方案)治疗。评估并比较两组患者临床疗效和不良反应。结果观察组患者疾病控制率为84.8%,高于对照组患者的69.7%,差异有统计学意义(P<0.05)。观察组患者恶心呕吐和粒细胞减少Ⅲ~Ⅳ度发生率分别为21.2%和15.2%,低于对照组的36.4%和33.3%,差异均有统计学意义(均P<0.05)。结论 FOLFOX一线化疗方案治疗失败的晚期大肠癌患者,采用周剂量伊立替康联合雷替曲塞作为二线治疗方案,临床效果能够显著提高,不良反应较低,具有较好的安全性。     

雷替曲塞联合伊立替康与FOLFIRI方案二线治疗晚期结直肠癌的近期疗效

目的:观察雷替曲塞联合伊立替康方案治疗晚期结直肠癌的近期疗效和安全性。方法:经病理组织学或细胞学确诊的 44例晚期结直肠癌患者随机分为对照组（22例)和实验组（22例)。对照组,伊立替康180mg/m2静滴90min d1,亚叶酸钙400mg/m2静滴d1,5-氟尿嘧啶400mg/m2静推d1,2000mg/m2静滴46h d1。实验组,伊立替康180mg/m2静滴90min d1,雷替曲塞3mg/m2静滴15min d1,21天为1周期,2周期后评价疗效。结果:对照组PR 3例、SD 5例、PD 14例,实验组PR 4例、SD 6例、PD 12例,两组均无CR病例。两组有效率(RR)分别为13.6%和18.2％,疾病控制率(DCR)分别为36.4％和45.5%（P>0.05)。对照组乏力、周围神经毒性、黏膜炎和脉管炎发生率分别为72.7%、31.8%、36.4%和27.3%(P<0.05),实验组血红蛋白减少发生率为59.1%(P<0.05)。结论:雷替曲塞联合伊立替康方案与FOLFIRI方案的近期疗效相当,但不良反应更轻,可以作为晚期结直肠癌的有效姑息治疗方案。     

雷替曲塞／贝伐珠单抗联合伊立替康或奥沙利铂方案治疗晚期结直肠癌的临床观察

目的 探讨含雷替曲塞／贝伐珠单抗的联合化疗方案在晚期结直肠癌二线及二线以上治疗中的疗效及安全性。方法 收集二线或二线以上治疗均采用含雷替曲塞／贝伐珠单抗联合伊立替康或奥沙利铂方案共15例晚期结直肠癌患者的资料,所有方案均以2周为1周期,其中采用雷替曲塞+贝伐珠单抗方案2例,雷替曲塞+贝伐珠单抗+伊立替康方案9例,雷替曲塞+贝伐珠单抗+奥沙利铂方案4例。贝伐珠单抗5mg／kg 静滴,d1;雷替曲塞2mg／m2静滴15min,d2;伊立替康180mg／m2静滴1h,d2;奥沙利铂85mg／m2静滴2h,d2。结果 15例患者均可评价疗效。获PR 2例,SD 10例,PD 3例,有效率为13.3％,疾病控制率为800％;中位无疾病进展时间为5.1个月（95％CI：3.404～6.813个月）,中位OS为11.5个月（95％CI：8.985～13.930个月）。毒副反应主要包括食欲减退、恶心呕吐、疲乏、白细胞减少和血小板减少等,3～4级毒副反应以食欲减退、恶性呕吐、疲乏和血小板减少为主。结论 含雷替曲塞／贝伐珠单抗联合伊立替康或奥沙利铂方案在晚期结直肠癌二线及二线以上治疗中的疾病控制率高,毒副反应可耐受,可推荐为Ⅲ期临床研究方案以及二线或二线以上晚期结直肠癌的治疗方案。     

雷替曲塞治疗结直肠癌的研究进展

雷替曲塞为抗代谢类叶酸类似物,是胸苷酸合成酶（TS）抑制剂,其代谢物对TS抑制作用更强且时间更长,抗细胞DNA合成更显著。研究证实其对多种实体瘤有抑制活性,适用于5-氟尿嘧啶/亚叶酸钙化疗不耐受及不适合的晚期结直肠癌患者。2012欧洲ESMO推荐雷替曲塞作为氟尿嘧啶化疗出现心脏毒性的标准替代药物。研究表明雷替曲塞单药方案治疗晚期结直肠癌不劣于5-氟尿嘧啶,联合方案疗效更好。因其安全性及临床疗效显示出明显优势,进一步联合靶向治疗将会成为雷替曲塞治疗结直肠癌新的研究方向及治疗选择。目前为止,雷替曲塞联合伊立替康及西妥昔单抗的研究正在进行中,本文就雷替曲塞治疗结直肠癌的相关研究及治疗进展作一综述分析。     

奥沙利铂一线治疗后再引入与雷替曲塞联合二线治疗晚期结直肠癌的临床观察*

目的:评估奥沙利铂一线用于治疗晚期结直肠癌后与雷替曲塞联合再引入二线治疗的疗效及安全性。方法:收集2010年5 月至2014年12月广西中医药大学附属瑞康医院收治的48例晚期结直肠癌患者,根据一线应用奥沙利铂的情况分为两组:A 组（一线使用不含奥沙利铂方案）20例;B 组（一线使用含奥沙利铂方案）28例。二线治疗方案:雷替曲塞3 mg/m2,静脉滴注,d1;奥沙利铂100～130 mg/m2,静脉滴注,d1;每21天1 次。结果:48例均可评价疗效,两组有效率分别为30.0%（6/ 20）、32.1%（9/ 28）;疾病控制率分别为80.0%（16/ 20）、75.0%（21/ 28）;中位无进展生存期分别为6.5 个月、7.0 个月;中位总生存期分别为10个月、13个月;两组有效率、疾病控制率、中位无进展生存期及中位总生存期比较差异均无统计学意义（P = 0.264,0.514,0.713,0.788）。 主要不良反应为骨髓抑制、转氨酶异常和胃肠道反应,以Ⅰ～Ⅱ级为主;两组感觉神经异常Ⅰ～Ⅱ级发生率相近。结论:奥沙利铂再引入联合雷替曲塞二线化疗对曾使用过奥沙利铂一线化疗的患者仍然有效,无耐药性,安全可行,对不能接受伊立替康二线治疗的晚期结直肠癌患者是较好选择。      

以雷替曲塞为基础的方案二线后治疗晚期结直肠癌的临床研究

目的：探讨以雷替曲塞为基础的二线后（含三线、四线、五线）化疗方案治疗以氟尿嘧啶为基础化疗方案治疗失败后的晚期结直肠癌患者的临床疗效及安全性。方法选择2013年4月至2014年3月在我院接受以雷替曲塞为基础的二线后化疗方案的晚期结直肠癌患者31例,入组患者均接受以雷替曲塞为基础的方案进行化疗,每2个周期评价疗效,至病情进展或不可耐受停止,并在治疗过程中观察患者的不良反应。结果31例患者完成治疗周期数共计99次,平均每人为3次。所有患者皆可评价疗效,其中部分缓解（partial response,PR）的患者1例（3.23%）,疾病稳定（stable disease,SD）者17例（54.84%）,疾病进展（progressive dis-ease,PD）者13例（41.94%）;客观有效率（objective response rate,ORR）为3.23%,临床获益率（clinical benefit rate,CBR）为58.06%。中位无进展生存时间（median progression free survival,mPFS）为1.53个月（95% CI：0.921～2.139）。无3～4度严重不良反应发生。结论以雷替曲塞为基础进行二线后化疗方案治疗晚期结直肠癌,CBR高,不良反应小,可以作为一种临床治疗手段。     

伊立替康联合替吉奥或5-氟尿嘧啶方案二线治疗晚期胃癌的疗效观察

目的 比较伊立替康联合替吉奥与伊立替康联合5-氟尿嘧啶二线治疗晚期胃癌的临床疗效及 不良反应。方法 77例既往应用含铂方案治疗失败的晚期胃癌患者随机分为两组,A组: 36例患者接 受伊立替康联合替吉奥胶囊的化疗方案,B组: 41例患者接受伊立替康联合5-氟尿嘧啶的化疗方案,按 照WHO标准评价客观疗效和不良反应。结果 患者经治疗后, A组总有效率为 41.7％, 最主要的不良反 应为血液学毒性, 表现为白细胞和血小板降低、贫血及腹泻等, 机体可以耐受这些不良反应。B组总有 效率为39.2% , 主要的不良反应为静脉炎、腹泻等。A组和B组中位疾病进展时间（TTP）分别为4.8月 和3.1月（P=0.001）。结论 两种联合化疗方案都具有较好的疗效, 相对来说,A组具有中位疾病进展 时间长和不良反应相对小的优点, 且住院时间短, 可作为既往应用含铂方案治疗失败的晚期胃癌患者的 二线化疗方案之一。     

雷替曲塞在120例结直肠癌肝转移治疗中的疗效分析

摘 要：［目的］ 评价雷替曲塞在治疗晚期结直肠癌肝转移中的疗效和不良反应。［方法］ 对120例结直肠癌术后肝转移的患者进行化疗,将其随机分为研究组和对照组,每组60例。研究组采用介入下肝动脉灌注雷替曲塞化疗联合栓塞治疗,对照组采用雷替曲塞单药静脉滴注治疗。以上治疗每3周1次。共进行3~6个周期。比较两组的治疗有效率（RR）、疾病控制率（DCR）、中位疾病进展时间、生存率及不良反应情况。［结果］ 治疗有效率（RR）研究组为38.3%,对照组为20.0%,差异有统计学意义（P=0.027);疾病控制率（DCR）研究组为66.7%,对照组为45.0%,差异有统计学意义（P=0.017）。中位疾病进展时间研究组为15.4个月,对照组为10.5个月,差异有统计学意义（P=0.000）。研究组1、2年生存率分别为71.7%、56.7%,对照组分别为51.7%、38.3%,差异均有统计学意义（P值分别为0.024、0.044）。［结论］ 介入下肝动脉灌注雷替曲塞化疗联合栓塞治疗结直肠癌肝转移疗效肯定,不良反应能耐受,值得临床推广。     

雷替曲塞单药二线治疗老年晚期结直肠癌的临床研究

目的 探讨雷替曲塞单药二线治疗老年晚期结直肠癌的疗效和安全性.方法 将57例老年晚期结直肠癌患者随机分为试验组(29例)和对照组(28例).试验组采用雷替曲塞单药方案化疗,对照组采用FOLFIRI方案化疗,观察并比较2组治疗效果及不良反应.结果 试验组与对照组的客观有效率(RR)分别为13.8%和17.9%,疾病控制率(DCR)分别为58.6%和53.6%,差异无统计学意义(P>0.05).2组中位无进展生存时间(PFS)分别为4.4个月和4.9个月,差异无统计学意义(P>0.05).试验组在恶心、呕吐及腹泻方面的不良反应明显低于对照组,差异有统计学意义(P<0.05).结论 雷替曲塞单药方案二线治疗老年晚期结直肠癌疗效与FOLFIRI方案相当,且安全性更高,使用更方便.     

Clinical observation of raltitrexed/bevacizumab combined with irinotecan or oxaliplation for advanced colorectal cancer简

Objective： The aim of the study was to investigate the efficacy and safety of raltitrexed/bevacizumab in combination with irinotecan or oxaliplation for advanced colorectal cancer as the second-line and second-line above treatments. Metho ods： Fifteen cases of advanced colorectal cancer were enrolled to receive regimens including raltitrexed/bevacizumab combined with irinotecan or oxaliplation. Two cases were treated with raltitrexed ＋ bavacizumab regimen, 9 cases with raltitrexed ＋ bavacizumab ＋ irinotecan regimen, and 4 cases with raltitrexed ＋ bevacizumab ＋ oxaliplation regimen. The doses of the drugs were as follows： bevacizumab 5 mg/kg ivgtt, d 1; raltitrexed 2.0 mg/m2 ivgtt 15 min, d2; irinotecan 180 mg/m2 ivgtt 1 h, d2; and oxaliplatin 85 mg/m2 ivgtt 2 h, d2. Two weeks was a cycle for each regimen. Results： The efficacy of the 15 patients could be evaluated. Two cases were in PR ,10 cases in SD, 3 cases in PD, the response rate was 13.3%, and the disease control rate was 80.0%. The median progress-free survival was 5.1 months （95% CI： 3.404-6.813 months）, and the median overall survival was 11.5 months （95% CI： 8.985-13.930 months）. The adverse effects included anorexia, nausea/vomiting, fatigue, leucopenia, thrombocytopenia, etc, and the main 3-4 grades adverse effects were anorexia, nausea/vomiting, fatigue, and thrombocytopenia. Conclusion： Raltitrexed/bevacizumab combined with irinotecan or oxaliplatin as the secondline and second-line above treatments for advanced colorectal cancer has high disease control rates, and the adverse effect is well tolerated. The combined regimen can be recommended as a phase III clinical research and second-line and secondlines above treatments for advanced colorectal cancer.     

Optimisation of irinotecan dose in the treatment of patients with metastatic colorectal cancer after 5-FU failure: results from a multinational, randomised phase II study

Although irinotecan 350 mg m(-2) is a standard option for relapsed/refractory advanced colorectal cancer, there is some evidence that suggests that a higher dose may be more effective, with acceptable tolerability, following 5-fluorouracil (5-FU). This study assessed the optimal dosing strategy for irinotecan, along with treatment efficacy and safety. A total of 164 patients with metastatic colorectal cancer progressing after failure on 5-FU or raltitrexed received either 350 mg m(-2) irinotecan (Group A; n=36) or 250, 350 or 500 mg m(-2), according to individual patient tolerance (Group B; n=62) or based on risk factor optimisation (Group C; n=66). There were no complete responses. There was a trend towards a higher overall response rate in Group B (13%) than in Groups A (8%) and C (9%). Tumour control growth rate was high in all three groups: 58% in group A, 60% in Group B and 50% in Group C. A total of 34% of patients in Group B and 9% in Group C were able to receive a dose of 500 mg m(-2). Median duration of response and time to progression were significantly longer in Groups A and B compared with Group C. No significant between-group differences for any adverse events were seen, although there was a small trend towards better tolerability in Group B. Individual dose escalation based on patient tolerance may allow more patients to receive a higher irinotecan dose without causing additional toxicity and can be an appropriate patient management strategy.     

Randomized multicenter phase II trial of oxaliplatin plus irinotecan versus raltitrexed as first-line treatment in advanced colorectal cancer.

PURPOSE: Irinotecan and oxaliplatin are two new agents with promising activity in advanced colorectal cancer. Based on preclinical and clinical evidence that both drugs act synergistically, a randomized phase II study was initiated to investigate the therapeutic potential and tolerance of this combination in the front-line setting. PATIENTS AND METHODS: Ninety-two patients with previously untreated, measurable disease were randomized to receive biweekly oxaliplatin 85 mg/m(2) plus irinotecan 175 mg/m(2) or raltitrexed 3 mg/m(2) given on day 1 every 3 weeks. Upon development of progressive disease, second-line treatment with the opposite arm was effected. RESULTS: Patients allocated to oxaliplatin/irinotecan had a significantly better radiologically confirmed response rate (43.5% v 19.6%; P =.0025) and longer progression-free survival (median, 7.1 v 5.0 months; P =.0033). Improvement in overall survival, however, did not reach the level of significance (median, 16.0 v 16.5 months; P =.3943). The response rate after cross-over was 33.3% (eight of 24) for assessable patients treated with oxaliplatin/irinotecan compared with 14.2% (three of 21) for those treated with second-line raltitrexed. Oxaliplatin/irinotecan caused more hematologic and gastrointestinal toxicities, necessitating dose reductions in 10 of the first 20 patients. After adjustment of the irinotecan starting dose from 175 to 150 mg/m(2), tolerance of treatment was acceptable; the most commonly encountered events (all grades) were neutropenia (81%), alopecia (65%), nausea/emesis (62%), peripheral sensory neuropathy (62%), and diarrhea (46%). CONCLUSION: Oxaliplatin/irinotecan seems beneficial as first-line therapy in advanced colorectal cancer, with an acceptable toxicity profile at the reduced irinotecan dose level. Its promising therapeutic potential is supported by the high response activity noted in the raltitrexed control arm after cross-over, which may also explain the lack of a difference in overall survival.     

Bimonthly leucovorin,infusion 5-fluorouracil,hydroxyurea, and irinotecan (FOLFIRI-2) for pretreated metastatic colorectal cancer

Irinotecan has shown activity in advanced colorectal cancer resistant to leucovorin and fluorouracil. Preclinical experiments on cell cultures and human tumor xenografts indicated potential synergy when combining irinotecan and fluorouracil. We designed a new regimen combining leucovorin, fluorouracil, irinotecan, and hydroxyurea (FOLFIRI-2) and conducted a phase II study to establish its efficacy and tolerance in advanced colorectal cancer refractory to fluorouracil and oxaliplatin. Treatment was repeated every 2 weeks and consisted of leucovorin 400 mg/m2 on day 1, immediately followed by 46 hours of continuous infusion of fluorouracil 2,000 mg/m2, irinotecan 180 mg/m2 on day 3, and hydroxyurea 1,500 mg the day before leucovorin, and on days 1 and 2. Treatment was continued until progression or limiting toxicity. Twenty-nine heavily pretreated patients entered the study. Five patients achieved an objective response (17%), and 12 obtained stabilization of disease or minor response (52%). Five patients failed to continue treatment (17%) because of toxicity or worsening condition. From the start of FOLFIRI-2 treatment, median progression-free survival was 4.1 months and median survival was 9.7 months. Grade III/IV National Cancer Institute-Common Toxicity Criteria toxicities were nausea 17%, diarrhea 31%, mucositis 14%, neutropenia 52%, and febrile neutropenia 14%. FOLFIRI-2 achieved a good rate of response and stabilization in heavily pretreated patients despite significant toxicity.     

A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer.

PURPOSE: Three agents with differing mechanisms of action are available for treatment of advanced colorectal cancer: fluorouracil, irinotecan, and oxaliplatin. In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease. PATIENTS AND METHODS: Patients were concurrently randomly assigned to receive irinotecan and bolus fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX). The primary end point was time to progression, with secondary end points of response rate, survival time, and toxicity. RESULTS: A total of 795 patients were randomly assigned between May 1999 and April 2001. A median time to progression of 8.7 months, response rate of 45%, and median survival time of 19.5 months were observed for FOLFOX. These results were significantly superior to those observed for IFL for all end points (6.9 months, 31%, and 15.0 months, respectively) or for IROX (6.5 months, 35%, and 17.4 months, respectively) for time to progression and response. The FOLFOX regimen had significantly lower rates of severe nausea, vomiting, diarrhea, febrile neutropenia, and dehydration. Sensory neuropathy and neutropenia were more common with the regimens containing oxaliplatin. CONCLUSION: The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe. It should be considered as a standard therapy for patients with advanced colorectal cancer.