西妥昔单抗联合化疗治疗转移性结直肠癌的临床观察

目的观察西妥昔单抗与奥沙利铂/5-FU/FA联合治疗转移性结直肠癌的近期疗效及毒性反应。方法对11例转移性结直肠癌(MCRC)患者采用西妥昔单抗与奥沙利铂/5-FU/FA化疗联合方案,应用2周期后评价近期疗效及毒性反应。西妥昔单抗首次推荐剂量为400 mg/m~2,以后每周剂量为250 mg/m~2,奥沙利铂/5-FU/FA化疗剂量采用FOLFOX4方案。结果11例患者均完成西妥昔单抗连续6周用药,奥沙利铂/5-FU/FA化疗2周期(每2周重复1次),无CR病例,2例PR(18.18%),4例SD(36.36%),5例PD(45.45%),疾病控制(PR SD)率54.55%。治疗过程中出现的毒性反应为3～4度的痤疮样皮疹,另外有恶心、呕吐、腹痛和虚弱,2～3度白细胞下降。全组患者无过敏反应。结论西妥昔单抗可提高肿瘤对放化疗的敏感性。采用西妥昔单抗与奥沙利铂联合治疗11例转移性结直肠癌患者,取得初步疗效和安全性观察,且不因联合化疗而增加毒性反应,耐受性良好。     

西妥昔单抗联合FOLFOX4方案治疗转移性结直肠癌的临床观察

<正>本文对我院收治的38例应用西妥昔单抗联合FOLFOX4方案治疗的转移性结直肠癌病例进行分析,以期对西妥昔单抗的临床应用积累一定的经验。1资料与方法1.1临床资料:2007年1月至2008年12月间我院收治的晚期结直肠癌(ACRC)患者38例,所有患者均有明确的病理学诊断,检测肿瘤K-ras基因状态,38例患者的肿瘤中K-ras基因     

西妥昔单抗联合FOLFOX化疗治疗转移性结直肠癌的临床研究

目的 观察西妥昔单抗联合FOLFOX化疗治疗转移性结直肠癌(MCRC)的近期疗效及不良反应。方法 48例确诊为MCRC患者为研究对象。西妥昔单抗每周给药,首剂负荷量为400 mg·m^-2,维持量为250 mg·m^-2;联合方案：奥沙利铂85 mg·m^-2+5-氟尿嘧啶600 mg·m^-2+亚叶酸钙200 mg·m^-2,2周为一个周期。完成两个周期的化疗以后,评价疗效,观察中位至疾病进展时间和不良反应。结果 完全缓解0例,部分缓解39例,疾病稳定9例,疾病进展0例,总有效率81.3%,疾病控制率100.0%,中位至疾病进展时间是9个月。不良反应主要为Ⅰ~Ⅱ级。结论 西妥昔单抗联合FOLFOX的化疗方案治疗MCRC可获得较高有效率,延长了疾病进展时间,改善了患者的生活质量,值得临床推广应用。     

西妥昔单抗联合化疗治疗晚期结直肠癌临床疗效观察

目的 观察西妥昔单抗联合化疗治疗晚期结直肠癌的疗效及毒副反应.方法 25例晚期结直肠癌,给予西妥昔单抗联合化疗治疗.结果 全组有效率56.0%,疾病控制率(DCR)88.0%.中位肿瘤进展时间(TTP)10.5个月.主要毒副反应为痤疮样皮疹.结论 西妥昔单抗联合化疗治疗晚期结直肠癌疗效较好,毒副反应可耐受.     

西妥昔单抗联合化疗方案治疗晚期结直肠癌的临床疗效

目的评价西妥昔单抗联合化疗方案治疗晚期结直肠癌的疗效及不良反应。方法选择我院2007年1月-2010年6月单用或联合化疗使用西妥昔单抗治疗晚期或转移性结直肠癌患者35例,采用RF,cISr 1.1版实体肿瘤客观疗效评定标准进行临床疗效评价。并采用美国毒性反应评价标准(CIE 3.0)进行不良反应评价。结果共有31例纳入疗效评价。其中完全缓解l例,部分缓解9例,疾病稳定14例,疾病进展7例,有效率32.3%,疾病控制率75.O%;K-RAS基因野生型的患者有效率(40.0%)明显高于未检测组(18.2%)。33例发生了不良反应,发生率94.3%,主要为I～Ⅱ级(占74.1%)。结论西妥昔单抗联合放化疗方案治疗晚期结直肠癌可获得较高有效率,延长了疾病进展时间。     

西妥昔单抗联合替吉奥治疗老年转移性结直肠癌的临床观察

目的 探讨西妥昔单抗联合替吉奥治疗老年转移性结直肠癌的疗效及安全性.方法 收集一线解救化学治疗(化疗)不能耐受及拒绝一线化疗方案的32例老年患者的临床资料.按K-Ras基因表型分为联合用药组(16例),对照组(16例).联合用药组患者采用西妥昔单抗联合替吉奥方案治疗,西妥昔单抗首次剂量为400mg/m2,以后每周剂量为250mg/m2,每周1次.替吉奥根据体表面积来确定初始剂量,体表面积＜1.25 m2,40mg;体表面积1.25～1.5 m2,50mg;体表面积＞1.5m2,60mg.用法:2次/d,早饭后和晚饭后分别口服1次,连续服用14d,停药7d,3周为1个周期;对照组根据体表面积服用相应剂量的西妥昔单抗.至少给予2个周期治疗.观察疗效及不良反应.结果 联合用药组完全缓解3例(18.75％),部分缓解4例(25.00％),病情稳定5例(31.25％),病情进展4例(25.00％),有效率43.75％ (7/16),疾病控制率75.00％(12/16).对照组完全缓解3例(18.75％),部分缓解3例(18.75％),病情稳定3例(18.75％),病情进展7例(43.75％),有效率37.50％ (6/16),疾病控制率56.25％(9/16).联合用药组的疾病控制率均优于对照组,差异均有统计学意义(P＜0.05);2组有效率比较,差异无统计学意义(P＞0.05).联合用药组和对照组常见的不良反应为色素沉着、皮疹,其发生率分别为87.50％ (14/16)和56.25％(9/16),恶心呕吐的发生率分别为62.50％(10/16)和56.25％(9/16).2组不良反应发生率差异无统计学意义(P＞0.05).结论 西妥昔单抗联合替吉奥治疗老年转移性结直肠癌较对照组更有效,不良反应可耐受.     

治疗转移性结直肠癌新药--西妥昔单抗

西妥昔单抗是一种嵌合型单克隆抗体,可与结直肠癌肿瘤细胞上的表皮生长因子受体(EGFR)特异性结合,从而诱导有益的细胞反应,提高肿瘤对放化疗的敏感性.西妥昔单抗已在瑞士和美国上市,治疗表达EGFR的转移性结直肠癌.推荐剂量为首次负荷量400 mg·m-2,每周维持剂量250 mg·m-2.西妥昔单抗单独治疗最常见的3/4级不良反应有痤疮样皮疹、虚弱、腹痛和恶心/呕吐等.     

尼妥珠单抗联合FOLFIRI化疗治疗术后复发转移性结直肠癌的临床观察

目的：观察和评价表皮生长因子受体（EGFR）的单克隆抗体尼妥珠单抗（nimotuzumab）联合FOLFIRI化疗治疗术后复发转移性结直肠癌的近期疗效和不良反应。方法：入组患者为经手术治疗后复发转移性结直肠癌患者17例,应用尼妥珠单抗联合伊立替康＋亚叶酸钙＋氟尿嘧啶两周方案（FOLFIRI）,尼妥珠单抗剂量200mg·m-1,每2周（200mg·m-1）1次维持。治疗4个周期后评价疗效。结果：全组17例完全缓解1例,部分缓解7例,稳定7例,进展2例,总有效率47．1％。不良反应主要是恶心呕吐、骨髓抑制、迟发性腹泻、胆碱能综合征等。结论：尼妥珠单抗联合FOLFIRI化疗治疗术后复发转移性结直肠癌疗效肯定,不良反应可耐受,可供临床安全使用。     

西妥昔单抗联合卡培他滨与奥沙利铂治疗晚期结直肠癌20例

目的 评价西妥昔单抗联合卡培他滨+奥沙利铂(XELOX方案)治疗晚期结直肠癌的临床疗效与安全性. 方法经病理组织学确诊为晚期结直肠癌患者共40例,分为治疗组和对照组各20例. 对照组单用XELOX方案:奥沙利铂130 mg.(m²)^-1,静脉滴注2 h,第1天,卡培他滨2 000 mg.(m²)^-1,bid,po,第1～14天,每3周重复,共2～4个周期;治疗组XELOX方案＋西妥昔单抗,西妥昔单抗首次给予负荷量400 mg.(m²)^-1静脉滴注2 h,此后每周维持量250 mg.(m²)^-1静脉滴注1 h. 观察其临床疗效与不良反应. 结果 治疗组与对照组总有效分别为12和7例,疾病控制分别为18和14例,中位疾病进展时间分别为7.7与5.4个月,差异均有统计学意义(P<0.05);治疗后主要为Ⅰ或Ⅱ度不良反应,治疗组痤疮样皮疹发生率55.0%. 结论 西妥昔单抗联合XELOX方案治疗老年晚期结直肠癌安全且疗效明显,不良反应能耐受,值得临床进一步研究.     

西妥昔单抗联合FOLFIRI方案治疗化疗耐药晚期结直肠癌临床疗效观察

目的观察西妥昔单抗联合FOLFIRI方案治疗化疗耐药晚期结直肠癌的近期疗效。方法全组共9例患者,均经病理组织学确诊,采用西妥昔单抗联合FOLFIRI方案治疗。结果其中PR2例,SD5例,PD2例,总有效率28.57%,疾病控制率71.43%,中位生存期18周。结论西妥昔单抗联合FOLFIRI治疗化疗耐药晚期结直肠癌,疗效较好,除痤疮样皮疹外,毒副作用无明显增加,晚期患者能适应。     

Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for wild-type KRAS metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines

The aim of this study is to prospectively evaluate the efficacy of combination chemotherapy with every second week cetuximab and irinotecan in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with wild-type KRAS metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. Cetuximab was administered at 500 mg/m(2) biweekly with irinotecan. The primary endpoint was response rate. The pharmacokinetics of cetuximab was also evaluated in 5 patients. From May 2009 to February 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 patients who were treated with biweekly cetuximab plus irinotecan, partial response was observed in 9 patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7%-49.4%) and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95% CI, 57.7%-90.0%). The median progression-free survival was 5.3 months and median overall survival was 10.8 months. Grade 3 skin toxicity was observed in 3 patients (10.0%) and one treatment related death due to pneumonia was observed. Combination chemotherapy with biweekly cetuximab and irinotecan was effective for pretreated metastatic colorectal cancer with wild-type KRAS.     

Cetuximab: in the treatment of metastatic colorectal cancer

Cetuximab is a chimeric monoclonal antibody highly selective for the epidermal growth factor receptor (EGFR), which is over-expressed by 25-80% of colorectal cancer tumours and associated with advanced disease. Cetuximab induces a broad range of cellular responses in tumours expressing EGFR, enhancing sensitivity to radiotherapy and chemotherapeutic agents. In a large, randomised, open-label, multicentre study in adult patients with irinotecan-refractory, metastatic colorectal cancer expressing EGFR, cetuximab 400 mg/m2 initial dose followed by 250 mg/m2 weekly plus irinotecan (various doses) produced a greater rate of partial response and disease control (partial response plus stable disease), and increased time to disease progression, compared with cetuximab monotherapy; survival was similar in both groups. The same dosage of cetuximab combined with irinotecan, fluorouracil and folinic acid (various regimens) produced partial responses in 43-58% of patients, a complete response in 5% of patients (one study only) and stable disease in 32-52% of patients with treatment-naive metastatic colorectal cancer expressing EGFR in three small, open-label trials. The most common grade 3/4 adverse events associated with cetuximab monotherapy were acne-like rash, asthenia, abdominal pain and nausea/vomiting. In patients receiving cetuximab plus irinotecan, these were diarrhoea, asthenia, leucopenia and neutropenia.     

Cetuximab: new drug. Metastatic colorectal cancer: an inappropriate evaluation

(1) In patients with metastatic colorectal cancer initially treated with irinotecan combination therapy, second-line therapy with a combination of fluorouracil, folinic acid and oxaliplatin resulted in a median survival time of 21 months after the start of first-line chemotherapy, in one clinical trial. (2) Cetuximab, an antibody directed against the epidermal growth factor receptor (EGFR), is indicated for patients with EGF-expressing metastatic colorectal cancer, after failure of irinotecan-based chemotherapy. (3) A comparative trial involving 329 patients showed that the cetuximab + irinotecan combination was more effective than cetuximab monotherapy in terms of progression-free survival time (4.1 versus 1.5 months). Three non comparative trials did not show that adding cetuximab to irinotecan improved the efficacy of irinotecan. (4) Nearly 90% of patients taking cetuximab developed cutaneous adverse effects (usually acne), which were severe in about 15% of cases. About 5% of cetuximab infusions were associated with occasionally severe hypersensitivity reactions. (5) More pertinent comparative trials are underway, but no detailed results were available on 29 April 2005. (6) The cetuximab packaging is somewhat impractical. (7) In practice, given its known toxicity and unproven efficacy, cetuximab currently has no place in the second-line treatment of colorectal cancer.     

Phase II study of second-line oxaliplatin, irinotecan and mitomycin C in patients with advanced or metastatic colorectal cancer

The aim of this phase II study was to investigate the therapeutic value of second-line treatment with oxaliplatin, irinotecan (CPT-11) and mitomycin C (MMC) in patients with metastatic colorectal cancer pretreated with 5-fluorouracil (5-FU)-based chemotherapy. A total of 10 patients with metastatic colorectal cancer, all of whom had developed progressive disease from advanced or metastatic colorectal cancer while receiving or within 6 months after discontinuing first-line chemotherapy with 5-FU and leucovorin, were entered in this study. At the time of relapse, cytotoxic chemotherapy consisting of oxaliplatin 80 mg/m2 plus CPT-11 80 mg/m2 given i.v. on therapeutic day 1, and MMC 6 mg/ m2 given i.v. on day 15, respectively, was initiated. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease. The overall response rate was 30% with three partial responses for all 10 assessable patients. Two additional patients (20%) had stable disease and five patients (50%) progressed. The median overall survival duration has not been reached yet and is longer than 7.1 months (range 2-23.5+) from the beginning of second-line therapy. Four patients are currently alive with progressive disease. The tolerance of second-line treatment was generally mild to moderate and easy to treat. Our data suggest that the combination of oxaliplatin, CPT-11 and MMC in patients with metastatic colorectal cancer pretreated with 5-FU-based chemotherapy is feasible and has substantial antitumor activity. Further evaluation of this regimen seems warranted.     

伊立替康联合氟尿嘧啶/亚叶酸钙治疗转移性结直肠癌

目的观察伊立替康联合亚叶酸钙及氟尿嘧啶方案治疗FOLFOX4方案失败的晚期结直肠癌的临床疗效及毒副反应。方法用CPT-11联合5-FU/CF方案治疗晚期结直肠癌患者28例,采用2周方案化疗,至少2个周期,即CPT-11180mg/m2静脉滴注,第1天;四氢叶酸200mg/m2静脉滴注,第1、2天;5-FU400mg/m2静脉推注,第1、2天;5-FU600mg/m2静脉滴注22h,第1、2天。按照WHO实体瘤近期客观疗效评定标准进行评价。结果全组28例患者均可评价疗效及不良反应。其中完全缓解0例,部分缓解10例,稳定9例,进展9例,有效率为35.7%。中位肿瘤进展时间TTP6.5个月,中位生存时间MST为12.5个月。不良反应主要是骨髓抑制,恶心、呕吐,脱发及延迟性腹泻。结论伊立替康联合5-FU/CF为二线治疗晚期结直肠癌安全有效的方案。     

Epidermal growth factor receptor monoclonal antibodies for the treatment of metastatic colorectal cancer

Treatment of metastatic colorectal disease has evolved over the last decade. Two epidermal growth factor receptor (EGFR) monoclonal antibodies--cetuximab and panitumumab--have been developed in an effort to provide yet another therapeutic option. The EGFR is a transmembrane glycoprotein, expressed constitutively throughout the body and found on many epithelial tissues. The monoclonal antibodies bind to and inhibit the activation of the receptor in the body. This inhibition prevents tumor cell growth, angiogenesis, invasion, and metastasis, and induces apoptosis. Cetuximab and panitumumab exhibit nonlinear pharmacokinetics. Both monoclonal antibodies are approved for the treatment of refractory metastatic colorectal cancer. Cetuximab in combination with irinotecan has significantly better response rates and progression-free survival compared with those of cetuximab or irinotecan alone. Cetuximab and panitumumab as monotherapy have shown significantly better response rates and progression-free survival compared with best supportive care in patients refractory to irinotecan and oxaliplatin. In the Cetuximab Combined with Irinotecan in First Line Therapy for Metastatic Colorectal Cancer (CRYSTAL) trial, treatment-na?ve patients received cetuximab in combination with the chemotherapy regimen infusional leucovorin, fluorouracil, and irinotecan (FOLFIRI) or FOLFIRI alone; the difference in progression-free survival was statistically significant but suggested only a modest benefit over FOLFIRI alone (8.9 vs 8 mo, p=0.036). Results of a preplanned analysis of the first 231 events in the Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) trial favored the control group (chemotherapy regimen with folinic acid [leucovorin], fluorouracil, and oxaliplatin [FOLFOX] plus bevacizumab) instead of the control group plus panitumumab. For clinical consideration, many trials have shown that the intensity or absence of EGFR expression is not a clinically significant predictor of outcomes. Development and intensity of a rash are suggested to be a positive predictor of outcomes in patients. The most common adverse events of EGFR monoclonal antibody therapy are rash, diarrhea, and hypomagnesemia. Other serious but not common adverse events include hypersensitivity reactions and pulmonary toxicity. The availability of EGFR monoclonal antibodies has provided another weapon in the arsenal to treat refractory metastatic colorectal cancer. They have shown safety and efficacy in combination with other chemotherapy regimens and as monotherapy; however, their use as metastatic colorectal cancer therapy needs to be further explored.     

奥沙利铂联合亚叶酸钙及氟尿嘧啶治疗晚期大肠癌的临床分析

目的观察奥沙利铂联合亚叶酸钙及氟尿嘧啶方案治疗晚期大肠癌的临床疗效及毒副反应。方法 64例晚期大肠癌患者给予化疗方案为:L-OHP 130 mg/m2静脉点滴2 h,d1;CF 200 mg/m2,静脉点滴2 h,d1;5-FU 400 mg/m2静脉推注,后2 400 mg/m2微泵持续静脉滴注48 h。每2周重复,4周为1个周期,完成2个周期后判定疗效,按WHO标准评价客观疗效和毒副反应。结果全组64例均可评价疗效,其中完全缓解8例,部分缓解24例,稳定18例,进展14例,总有效率CR+PR=50.0%。中位肿瘤进展时间为5.6个月,中位生存时间为9.5个月。毒副反应主要是骨髓抑制、胃肠道反应及外周神经毒性。结论奥沙利铂联合亚叶酸钙及氟尿嘧啶方案治疗晚期肠癌患者的近期疗效较好,毒副反应可以耐受,值得进一步研究应用。     

伊立替康联合5-氟尿嘧啶/亚叶酸钙双周方案治疗晚期结直肠癌的临床观察

目的:观察伊立替康(CPT-11)联合5-氟尿嘧啶(5-Fu)/亚叶酸钙(LV)方案治疗晚期结直肠癌的疗效及毒副反应。方法:全组31例,可评价疗效者30例,全部采用双周方案:CPT-11180mg·m-2静脉滴注,第1天;LV200mg·m-2静脉滴注,第1、2天;5-Fu400mg·m-2静脉推注,随后5-Fu600mg·m-2静脉滴注22h,第1、2天。14d为1个周期,3个周期(6周)评价疗效。结果:完全缓解1例,部分缓解11例,缓解率达40%;疾病稳定14例,疾病进展4例。中位疾病进展时间为6.5个月,中位生存期为13.9个月。主要毒副反应为迟发性腹泻(Ⅲ/Ⅳ度发生率为30%)及中性粒细胞减少(Ⅲ/Ⅳ度发生率为26.6%)。结论:CPT-11联合5-Fu/LV方案治疗晚期结直肠癌有效率高,毒副反应可以耐受,可作为晚期结直肠癌的一线或二线化疗方案。