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。     

雷替曲塞联合伊立替康治疗一线方案失败或术后复发转移胰腺癌的疗效

目的探讨雷替曲塞联合伊立替康治疗一线方案失败或术后复发转移的胰腺癌的临床疗效。方法选择70例吉西他滨治疗失败或手术复发转移的胰腺癌患者作为研究对象,给予雷替曲塞和伊立替康联合治疗,采用实体瘤疗效评价标准(RECIST)3.0评价近期疗效;观察肿瘤进展时间(TTP)和不良反应。结果全组患者的临床有效率为45.7%,疾病控制率为88.6%。患者不良反应主要表现为中性粒细胞减少、胃肠道反应、疲乏,多为1~2级。全组患者的TTP为(7.2±1.1)个月。结论雷替曲塞联合伊立替康治疗一线方案失败或手术后复发转移的胰腺癌患者具有一定临床疗效,不良反应轻,可延长患者生存时间。     

雷替曲塞或氟尿嘧啶联合伊立替康二线治疗晚期结直肠癌疗效分析

目的 观察雷替曲塞或氟尿嘧啶联合伊立替康二线治疗晚期结直肠癌的近期疗效和不良反应。方法 对蚌埠医学院第一附属医院收治的52例经一线FOLFOX方案治疗失败的晚期结直肠癌患者进行二线治疗。A组（25例）化疗方案为雷替曲塞联合伊立替康,B组（27例）化疗方案为氟尿嘧啶联合伊立替康及亚叶酸钙,比较两组二线治疗的临床疗效、不良反应及生存情况。结果 A组和B组有效率分别为36%和11.5%,差异有统计学意义（P﹤0.05）,疾病控制率分别为76.0%和57.7%,差异无统计学意义（P>0.05）,中位疾病进展时间分别为6.0月和4.5月,差异无统计学意义（P>0.05）。结论 雷替曲塞联合伊立替康方案二线治疗晚期结直肠癌疗效肯定,不良反应能耐受,使用方便,值得临床上推荐使用。     

伊立替康联合替吉奥二线治疗晚期胃癌临床观察

目的 观察伊立替康联合替吉奥二线治疗晚期胃癌的疗效及不良反应.方法 39例一线化疗失败的晚期胃癌患者,用伊立替康联合替吉奥方案进行二线治疗.结果 39例患者均可评价疗效,其中CR 0例,PR 14例,SD 15例,PD 10例,有效率为35.90％,疾病控制率为74.36％.主要不良反应为恶心、呕吐、腹泻、骨髓抑制等.结论 伊立替康联合替吉奥二线治疗晚期胃癌近期疗效较好,不良反应可耐受,是晚期胃癌二线治疗可选择的化疗方案.     

伊立替康联合顺铂治疗复发转移性卵巢癌

目的：观察伊立替康联合顺铂治疗复发转移性卵巢癌的疗效与安全性。方法：对11例复发性卵巢癌应用伊立替康200mg／m^2,静滴,第1天;顺铂25mg／m^2,静滴,第1—3天,21天为1个周期,2个周期后进行一次疗效评价。结果：11例患者中完全缓解1例,部分缓解6例,总有效率为63．6％;主要不良反应为血液毒性,Ⅲ-Ⅳ度中性粒细胞下降36．3％（4／11）,其次为恶心、呕吐,Ⅲ-Ⅳ度恶心、呕吐为27．3％（3／11）,仅1例出现Ⅲ度腹泻。结论：伊立替康联合顺铂治疗复发转移性卵巢癌是可行、安全、有效的。     

雷替曲塞联合伊立替康2周方案对比FOLFIRI方案二线治疗晚期结直肠癌的疗效观察

目的 观察雷替曲塞联合伊立替康2周方案治疗转移性结直肠癌的有效性和安全性。方法 经病理组织学或细胞学确诊的50例晚期转移性结直肠癌患者分为试验组（n=25）和对照组（n=25）。试验组方案： 雷替曲塞 2.5mg／m² 静滴,d₁;伊立替康（CPT-11） 180mg／m² 静滴,d₁。对照组方案：CPT-11 180mg／m² 静滴90min,d₁;亚叶酸钙 400mg／m² 静滴,d₁;5-FU 400mg／m² 静滴,d₁;5-FU 2400mg／m² 持续静滴46～48 h,d₁、d₂。两方案均2周为1周期,每周期评价毒副反应,每3个周期评价疗效,直至疾病进展或毒性不能耐受,最多治疗12个周期。结果 试验组获CR 1例,PR 4例,SD 18例,PD 2例;对照组获PR 2例,SD 19例,PD 4例。两组有效率（RR）分别为20％和8％,疾病控制率（DCR）分别为92％和84％,差异均无统计学意义（P＞0.05）。试验组1、2级转氨酶升高的发生率为24％,高于对照组的4％（P＜0.05）;对照组1、2级中性粒细胞减少、口腔黏膜炎的发生率均高于试验组（48％ vs. 20％,32％ vs. 8％,P＜0.05）。结论 雷替曲塞联合伊立替康2周方案与FOLFIRI方案的近期疗效相当,但毒副反应更轻,可以作为转移性结直肠癌的有效姑息治疗方案。     

伊立替康联合替吉奥二线治疗转移性大肠癌的临床观察

目的：研究伊立替康联合替吉奥二线治疗转移性大肠癌的临床疗效及不良反应.方法：对经病理检查确诊同时影像学证实有一个或一个以上脏器转移的36例转移性大肠癌患者,采用伊立替康联合替吉奥方法治疗.替吉奥胶囊80mg/（m2·d）,早、晚餐后口服,d1-14.伊立替康60mg/m2,第1、8天.每3周重复,2个周期后评价疗效同时记录不良反应.结果：全组36例病例中CR 2例（5.56％）,PR 11例（30.56％）,SD 10例（27.78％）,PD 13例（36.11％）,总有效率36.11％.主要不良反应为乙酰胆碱综合症、延迟性腹泻、中性粒细胞减少、胃肠道反应等,无治疗相关性死亡.结论：伊立替康联合替吉奥二线治疗转移性大肠癌有效率较好,不良反应可耐受,是转移性大肠癌患者较为理想的化疗方案.     

伊立替康联合顺铂治疗晚期胃癌的临床观察

目的　观察伊立替康联合顺铂治疗晚期胃癌的疗效及毒副反应。方法　３２例初治或复治晚期胃癌患者使用伊立替康和顺铂方案化疗。伊立替康１５０～１８０ｍｇ／ｍ２,静滴９０ｍｉｎ,ｄ１;顺铂２５ｍｇ／ｍ２,静滴,ｄ１～ｄ３。２１天为１周期,至少完成２个周期。结果　３２例均可评价疗效,获ＣＲ１例（３.１％）,ＰＲ１１例（３４.４％）,ＳＤ１１例（３４.４％）,ＰＤ９例（２８.１％）,有效率为３７.５％（１２／３２）。中位疾病进展时间为６.８个月,中位生存时间为１２.４个月。主要毒副反应为恶心、呕吐、迟发性腹泻、乙酰胆碱综合征、中性粒细胞减少等,多为１～２级。结论　伊立替康联合顺铂是晚期胃癌初治或复治患者的有效治疗方案,不良反应可耐受,值得临床进一步研究。     

伊立替康联合顺铂与拓扑替康联合顺铂二线治疗小细胞肺癌的比较研究

目的：回顾性观察伊立替康联合顺铂（IP组）与拓扑替康联合顺铂（TP组）二线治疗难治型小细胞肺癌的近期、远期疗效及毒副作用。方法：共62例患者，均为一线EP方案治疗失败且在3～6个月内出现进展，IP组：伊立替康60mg／m^2，第1、8天，DDP25mg／m^2，第1～3天，静脉滴注；TP组：拓扑替康0．75mg／m^2，第1—5天，DDP25mg／m^2，第1～3天，静脉滴注。均21天为1周期。每2个周期评价疗效。结果：IP组30例，有效率33，3％（10／30），TP组32例，有效率37．5％（12／32），两组近期疗效无差异（P〉0．05）。两组中位疾病进展时间（mTFP）均为3．0个月；中位生存期（MST）分别为12个月和11．5个月，无显著性差异（P〉0．05）。两组毒副作用主要表现为：Ⅲ-Ⅳ度粒细胞下降TP组高于IP组（31．3％vs．23．3％），但两组无显著性差异（P〉0．05）；Ⅲ-Ⅳ度血小板下降TP组高于IP组（18．8％vs．6．6％），两组有显著性差异（P〈0．05）；延迟性腹泻IP组高于TP组（30．0％vs．3．1％）。结论：伊立替康联合顺铂与拓扑替康联合顺铂二线治疗难治型小细胞肺癌均取得较好疗效，两方案毒副作用均可以耐受。     

伊立替康联合卡培他滨治疗晚期结直肠癌的临床观察

目的观察伊立替康联合卡培他滨治疗晚期结直肠癌的疗效和安全性。方法回顾性分析62例复发或转移性结直肠癌患者,接受伊立替康联合卡培他滨治疗：伊立替康125mg／m^2 d1、d8、d15静脉滴注90min;卡培他滨（希罗达）2500mg/m^2,分早晚2次,第1—14天,每28天重复。治疗至少2个周期,按照WHO标准进行疗效和不良反应评价,并观察至疾病进展时间及总生存期。结果62例患者中,可评价疗效的有59例。其中一线治疗28例,RR42．8％,DCR71．4％,TTP 8．6个月,MST18．8个月;二线治疗31例,RR32．3％,DCR61．2％,TTP 7．2个月,MST13．2个月。不良反应主要为恶心与呕吐、迟发性腹泻、粒细胞减少,多为Ⅰ-Ⅱ度,且一线和二线治疗的不良反应无统计学差异。结论伊立替康联合卡培他滨治疗晚期结直肠癌疗效高,不良反应可耐受,值得扩大样本进一步观察。     

Second-Line Treatment of Advanced Colorectal Cancer with a Biweekly Oxaliplatin plus Irinotecan Combination Regimen

BACKGROUND: Both oxaliplatin and irinotecan have demonstrated antitumor activity in pretreated colorectal cancer; experimental and early clinical data suggest that these two drugs may act synergistically. The aim of this study was to document the therapeutic index of a biweekly combination regimen in patients with metastatic colorectal cancer failing prior palliative first-line chemotherapy with raltitrexed. PATIENTS AND METHODS: In this study 27 patients with metastatic colorectal cancer were analyzed, who progressed while on or within 6 months after discontinuation of palliative first-line chemotherapy with raltitrexed. They received oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2) both given on days 1 and 15 every 4 weeks. RESULTS: The confirmed overall response rate was 37% (95% confidence interval, 19.4-57.7%), including 2 complete and 8 partial remissions. 12 additional patients (44.4%) had stable disease, and in only 5 cases (18.5%) disease progression was not influenced by chemotherapy. The median progression-free survival for all 27 patients was 8 months (range, 1-16+ months), and 16 patients (59%) are still alive after a median follow-up time of 12.5 months. Hematologic adverse reactions, specifically leukocytopenia and neutropenia, were common though generally mild to moderate with grade 4 toxicity occurring in only 2 cases. The most frequent non-hematologic adverse events included gastrointestinal symptoms; severe nausea/emesis and diarrhea, however, were noted in only 2 and 3 patients, respectively. CONCLUSIONS: Our data suggest that the described biweekly combination regimen of oxaliplatin and irinotecan has substantial antitumor activity in patients with progressive, raltitrexed-pretreated metastatic colorectal cancer. Because of its favorable toxicity profile, further evaluation of this combination seems warranted.     

Second-line treatment of advanced gastric cancer with oxaliplatin plus raltitrexed

BACKGROUND: Treatment with oxaliplatin plus raltitrexed has demonstrated an encouraging therapeutic index in patients with advanced colorectal cancer and malignant pleural mesothelioma. The aim of this multi-institutional study was to determine the antitumor potential of this combination in patients with metastatic gastric cancer failing prior palliative first-line chemotherapy, and to reconfirm its favorable toxicity profile. PATIENTS AND METHODS: 21 patients with metastatic gastric cancer, who progressed while on or within 6 months after discontinuing palliative first-line chemotherapy, participated in this study. They received raltitrexed 3,0 mg/m(2) and oxaliplatin 130 mg/m(2) both given intravenously on day 1 every 3 weeks. RESULTS: One patient achieved a partial response, 6 had stable disease, and 14 patients progressed. Median progression-free and overall survival from the onset of salvage chemotherapy was 2.0 and 4.5 months, respectively. Hematologic adverse reactions, specifically neutropenia and anemia were common, though generally mild to moderate with only 3 patients experiencing grade 3/4 toxicity. The most frequent non-hematologic adverse events included nausea/emesis, asthenia, and transient elevation of liver functional parameters, again with grade 3 symptoms occurring only in a minority of patients. CONCLUSION: Despite reproducibility of a favorable toxicity profile of oxaliplatin + raltitrexed, our data suggest that this combination regimen has no substantial antitumor activity in patients with progressive, chemotherapeutically pretreated metastatic gastric cancer.     

First-line treatment with irinotecan and raltitrexed in metastatic colorectal cancer. Mature results of a multicenter phase II study

OBJECTIVES: The combination of irinotecan and raltitrexed is safe and active in 5-fluorouracil-refractory, metastatic colorectal cancer (CRC), with the advantage of its convenient three-weekly schedule. The aim of this multicenter phase II study was to assess its efficacy and toxicity in first-line treatment. METHODS: Between May 2000 and March 2001, 62 previously untreated patients received irinotecan (350 mg/m(2)) plus raltitrexed (3 mg/m(2)), with courses repeated every 21 days. Objective response was assessed every three courses, and treatment maintained until tumor progression or unacceptable toxicity. RESULTS: A total of 331 cycles were administered, with a median of five cycles per patient (range, 1-16). Seventeen patients achieved a partial response and 2 a complete response, for an overall intention-to-treat response rate of 30% (95% confidence interval, 18-44%). The incidence of grade 3-4 toxicity per patient was diarrhea (27%), emesis (13%), anemia (12%), neutropenia (9%), and asthenia (7%). Three patients (5%) died from treatment-related adverse events (diarrhea plus neutropenia). The median potential follow-up is now 37 months. Median survival was 12.2 months, and median time to progression was 6.3 months. CONCLUSIONS: The combination of irinotecan plus raltitrexed is an easy comfortable schedule for patients with metastatic CRC, but both efficacy and toxicity results seem suboptimal for first-line treatment.     

重组人血管内皮抑制素和沙利度胺联合化疗治疗转移性结直肠癌的临床观察

目的 观察重组人血管内皮抑制素（恩度）、沙利度胺与细胞毒药物联合治疗晚期结直肠癌的疗效和安全性。方法 研究纳入47例2006年1月至2013年1月于中国医学科学院肿瘤医院接受恩度、沙利度胺联合细胞毒药物治疗的转移性结直肠癌患者。分别按照实体瘤的疗效评价标准（RECIST）1.0和国立癌症研究所毒性判定标准（NCI-CTC）4.0评价疗效和毒副反应,同时随访其生存情况。具体给药方案：恩度15 mg/d,加入生理盐水500 ml静脉滴注,d1~d10;沙利度胺150 mg或200 mg,每晚睡前顿服,d1~d10;14 d为1周期。与恩度和沙利度胺联用的化疗方案均为双周方案,包括奥沙利铂+氟尿嘧啶类药物（18例）,奥沙利铂+雷替曲塞（1例）,伊立替康+氟尿嘧啶类药物（26例）及伊立替康+雷替曲塞（2例）。结果 一线、二线、三线及三线以上接受含恩度+沙利度胺联合化疗方案者的中位生存期依次为26.1（95%CI： 21.9~30.2）、15.3（95%CI：9.5~21.0）和7.5（95%CI：4.2~10.7）个月,中位无进展生存期依次为：11.1（95%CI：8.6~13.7）、7.9（95%CI：4.7~11.2）和4.2（95%CI：1.5~7.0）个月,有效率依次为63.1%、37.5%和16.7%,疾病控制率依次为84.2%、68.7%和66.7%。全组的常见不良反应多为1~2级,包括白细胞减少、中性粒细胞减少、贫血、恶心和呕吐,3、4级毒副反应包括中性粒细胞减少（8.5%）、血小板减少（6.4%）、恶心（4.3%）、呕吐（4.3%）、便秘（4.3%）、疲乏（2.1%）和周围神经毒性（2.1%）。结论 恩度、沙利度胺联合细胞毒药物对初治和复治的转移性结直肠癌患者有较好的疗效及安全性。     

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。      

多西他赛联合吉西他滨治疗复发转移性乳腺癌临床疗效及预后影响因素

目的 探讨多西他赛联合吉西他滨治疗复发转移性乳腺癌的临床疗效及预后影响因素.方法 复发转移性乳腺癌患者46例,给予多西他赛联合吉西他滨治疗,具体方案为:多西他赛75 mg/m2,静脉滴注1h,第1天;吉西他滨1000 mg/m2,静脉滴注30 min,第1、8天;21 d为1个周期,评价患者近期疗效并随访患者总生存时间和无进展生存时间.采用单因素x2检验和多因素Cox风险比例模型分析患者临床病理特征与总有效率和总生存时间的关系.结果 46例复发转移性乳腺癌患者均接受3～6个周期的联合化疗治疗,完全缓解4例(8.7％),部分缓解22例(47.8％),稳定12例(26.1％),进展8例(17.4％),总有效率为56.5％ (26/46),疾病控制率为82.6％ (38/46);中位总生存时间为16.0个月(95％ CI为6.5 ～25.5个月),中位无进展生存时间为8.0个月(95％ CI为6.2～9.8个月);单因素分析结果显示,患者年龄、绝经状态、行为状况(PS)评分、肿瘤转移数目均与患者总有效率相关(P＜0.05),多因素Cox风险比例模型分析显示,患者年龄、绝经状态、PS评分、肿瘤转移数目均与患者的总生存时间相关,是患者预后的影响因素(P＜0.05);主要不良反应以骨髓抑制、胃肠道反应、皮疹、脱发及乏力为主,大多数为Ⅰ～Ⅱ级.结论 多西他赛联合吉西他滨治疗复发转移性乳腺癌的临床疗效好,安全性高;患者年龄、绝经状态、PS评分、肿瘤转移数目可作为该方案预后的影响因素.     

Availability of irinotecan in a second-line setting confers survival benefit to patients with advanced gastric cancer refractory to fluoropyrimidine-based regimens

Optimal second-line chemotherapy may contribute to favorable survival in patients who receive first-line treatment for advanced gastric cancer. The aim of this retrospective study was to compare a second-line setting using irinotecan with paclitaxel in terms of survival benefit and safety. A total of 179 patients with recurrent or unresectable gastric cancer who had received prior chemotherapy with a fluoropyrimidine-based regimen were treated with irinotecan alone at 150 mg/m(2) on days 1 and 15 every 4 weeks (Cohort I) or weekly paclitaxel at 80 mg/m(2) on days 1, 8 and 15 every 4 weeks (Cohort P) between April, 2004 and March, 2009. Patient characteristics, overall response rate, disease control rate, progression-free survival, overall survival and safety were investigated. Of the 179 patients, 92 received irinotecan and 87 patients who were contraindicated for irinotecan received weekly paclitaxel. The overall response and disease control rates in Cohort I were 6.5 and 43.5%, respectively, as compared with 9.8 and 54.9%, respectively, in Cohort P. No variation was noted in median progression-free survival (Cohort I vs. P, 2.6 vs. 2.8 months; P=0.812), whereas median overall survival (Cohort I vs. P, 9.8 vs. 4.9 months; P<0.0001) differed significantly between the two cohorts. The most common grade 3/4 adverse events were neutropenia, leukopenia, anemia and anorexia, which were tolerable in each treatment cohort. Availability of irinotecan in a second-line setting confers a survival benefit to advanced gastric cancer patients in whom fluoropyrimidine-based first-line chemotherapy was unsuccessful.     

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.     

Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma

There is no established second-line treatment for advanced pancreatic cancer after gemcitabine failure. In view of the urgent need for such therapy, and since preclinical and phase I clinical data suggest an encouraging, potentially synergistic activity between raltitrexed and irinotecan, the present randomised phase II study was initiated. A total of 38 patients with metastatic pancreatic adenocarcinoma, who progressed while receiving or within 6 months after discontinuation of palliative first-line chemotherapy with gemcitabine, were enrolled in this study. They were randomised to 3-weekly courses of raltitrexed 3 mg x m(-2) on day 1 (arm A) or irinotecan 200 mg x m(-2) on day 1 plus raltitrexed 3 mg x m(-2) on day 2 (arm B). The primary study end point was objective response, secondary end points included progression-free survival (PFS) and overall survival (OS), as well as clinical benefit response in symptomatic patients (n=28). In the combination arm, the IRC-confirmed objective response rate was 16% (three out of 19 patients had a partial remission; 95% CI, 3-40%), which was clearly superior to that in the comparator/control arm with raltitrexed alone, in which no response was obtained. Therefore, the trial was already stopped at the first stage of accrual. Also, the secondary study end points, median PFS (2.5 vs 4.0 months), OS (4.3 vs 6.5 months), and clinical benefit response (8 vs 29%) were superior in the combination arm. The objective and subjective benefits of raltitrexed+irinotecan were not negated by severe, clinically relevant treatment-related toxicities: gastrointestinal symptoms (42 vs 68%), partial alopecia (0 vs 42%), and cholinergic syndrome (0 vs 21%) were more commonly noted in arm B; however, grade 3 adverse events occurred in only three patients in both treatment groups. Our data indicate that combined raltitrexed+irinotecan seems to be an effective salvage regimen in patients with gemcitabine-pretreated pancreatic cancer. The superior response activity, PFS and OS (when compared to raltitrexed), as well as its tolerability and ease of administration suggest that future trials with this combination are warranted.     

阿帕替尼联合依托泊苷治疗三阴性乳腺癌的疗效及不良反应

目的探讨甲磺酸阿帕替尼联合依托泊苷治疗晚期、复发、难治性三阴性乳腺癌的疗效及不良反应。方法收集10例晚期复发难治性三阴性乳腺癌患者的临床资料,均接受甲磺酸阿帕替尼联合依托泊苷治疗,观察用药后疾病控制率(DCR)、客观缓解率(ORR)、无进展生存期(PFS)并记录不良反应。结果10例患者均接受了至少2个周期的治疗,无完全缓解病例,部分缓解4例,疾病稳定5例,疾病进展1例,ORR为40%(4/10),DCR为90%(9/10),中位PFS为4.0个月(95%CI:1.15~6.85)。阿帕替尼联合依托泊苷作为二线治疗方案治疗晚期复发难治性三阴性乳腺癌患者的中位PFS为4.0个月,与作为二线以上治疗方案的3.0个月比较,差异无统计学意义(P﹥0.05)。阿帕替尼联合依托泊苷治疗2个部位转移三阴性乳腺癌患者的中位PFS为4.0个月,与治疗2个以上部位转移患者的7.0个月比较,差异无统计学意义(P﹥0.05)。10例三阴性乳腺癌患者最常见治疗相关不良反应为中性粒细胞减少,发生率为50.0%,不良反应以1~2级为主,仅发生1例3~4级不良反应,经对症治疗后好转,无治疗相关死亡。结论甲磺酸阿帕替尼联合口服依托泊苷化疗对晚期复发难治性三阴性乳腺癌有一定疗效,不良反应可控。