FOLFOX4与FLP方案在食管胃结合部癌辅助化疗中的疗效比较

目的:回顾性分析辅助化疗FOLFOX4方案与FLP方案治疗食管胃结合部癌根治术后患者的疗效和不良反应。方法:回顾性分析2007年3月-2009年10月共123例接受FOLFOX4方案(67例)或FLP方案(56例)辅助化疗的食管胃结合部癌根治术后患者。主要评价指标为无病生存期(disease-free survival,DFS)、总生存期(overall survival,OS)和不良反应。同时,对两组患者的疗效进行分层分析。结果:FOLFOX4方案组和FLP方案组的中位DFS分别为35.9和16.8个月(P=0.008),中位OS分别为41.3和25.6个月(P=0.013)。分层分析显示,男性、45～65岁、腺癌以及Ⅱ期或ⅢA期患者接受FOLFOX4方案术后辅助化疗较FLP方案更具生存优势。FOLFOX4和FLP方案均耐受良好,血液学不良反应发生率无明显差异。FOLFOX4方案组非血液学不良反应主要为外周神经毒性,FLP方案组主要为消化系统反应。结论:与FLP方案相比,FOLFOX4方案辅助化疗可明显延长食管胃结合部癌术后患者的DFS和OS,且不良反应可耐受。     

贝伐珠单抗联合双周方案一线治疗晚期大肠癌的疗效及与K-ras基因的关系

目的:探讨贝伐珠单抗（BEV）联合双周方案一线治疗晚期大肠癌的临床疗效及与K-ras基因的关系。方法:收集2008年1月至2014年2月解放军总医院收治、经病理确诊的46例K-ras基因状态明确的晚期大肠癌患者临床资料,其中K-ras野生型23例、K-ras突变型23例;回顾性分析了BEV联合FOLFIRI（20例）或FOLFOX（26例）方案在一线治疗晚期大肠癌中的疗效及毒副反应的情况,并分析K-ras基因突变与疗效的关系。结果:46例均可评价近期疗效,总ORR为39.1%,总DCR为91.3%,总中位PFS为7.5个月。以化疗方案分组,其中FOLFIRI+BEV组ORR为30.0%,DCR为95.0%,中位PFS为8.1个月;FOLFOX+BEV组ORR为46.2%,DCR为88.5%,中位PFS为6.5个月。以K-ras基因状态分组,K-ras突变组ORR为30.4%,DCR为91.3%,中位PFS为6.2个月;K-ras野生组ORR为47.8%,DCR为91.3%,中位PFS为9.9个月。以上差异均无统计学意义（P＞0.05）。结论:虽然K-ras突变组在近期、远期疗效低于K-ras野生组,但在两组中均可见应用BEV能获益,同时再次证实K-ras基因突变是患者预后不良因素之一,但不是BEV应用的禁忌症;在化疗方案方面,BEV联合FOLFIRI或FOLFOX标准双周方案可提高化疗的ORR及DCR,且毒副反应小,安全性较好。     

FOLFIRI与FOLFOX4方案一线治疗晚期大肠癌的疗效观察

[目的]比较FOLFIRI方案与FOLFOX4方案一线治疗晚期大肠癌的疗效和不良反应。[方法]将56例晚期大肠癌患者随机分为两组:FOLFIRI方案组(n=28)和FOLFOX4方案组(n=28),2个周期后观察疗效和不良反应。[结果]FOLFIRI组有效率(RR)为35.7%,中位肿瘤进展时间(TTP)为7.5个月,中位总生存期(mOS)为15个月,1、2、3年生存率分别为89.29%、73.08%和40.00%;FOLFOX4组RR为39.3%,TTP为7.5个月,mOS为16个月,1、2、3年生存率分别为89.29%、72.00%和45.45%;两组比较各项指标差异无统计学意义(P>0.05)。不良反应中FOLFIRI组腹泻发生率高于FOLFOX4组,神经毒性发生率明显低于FOLFOX4组。[结论]FOLFIRI方案与FOLFOX4方案的疗效相当,都可作为晚期大肠癌的一线标准方案。     

Ki-67阳性或阴性表达乳腺癌不同辅助治疗方案的远期疗效比较

目的 探讨不同Ki-67表达情况下,乳腺癌术后不同辅助化疗方案及辅助化疗后接受不同内分泌药物治疗的远期疗效。方法 收集2008年1月至2009年12月694例乳腺癌患者,术后均接受蒽环类或蒽环类序贯紫杉类方案化疗;再选取其中ER阳性且绝经的261例患者,均接受选择性雌激素受体调节剂（SERM）或芳香化酶抑制剂（AI）内分泌治疗。对Ki-67不同表达情况下,不同辅助化疗方案及辅助化疗后不同内分泌药物治疗与无病生存期（DFS）和总生存期（OS）的关系进行分析。结果（1） 527例Ki-67阳性乳腺癌患者的中位DFS和OS分别为37.0个月和38.0个月,其中蒽环类方案组和序贯紫杉类方案组的中位DFS分别为36.5个月和38.0个月（P=0.046）,OS分别为38.0个月和39.0个月（P=0.045）;167例Ki-67阴性患者的中位DFS和OS分别为49.4个月和51.5个月,蒽环类方案组和序贯紫杉类方案组的中位DFS和OS差异均无统计学意义。在Ki 67和ER表达的4种组合中,仅Ki-67+ER-表达组蒽环类方案与序贯紫杉类方案的中位DFS（30.5个月vs.35.9个月,P=0.030）和中位OS（39.2个月vs.42.1个月,P=0.160）的差异有统计学意义。（2）261例ER阳性且绝经的患者中,200例Ki-67阳性者的中位DFS和OS分别为38.0个月和39.0个月,另外61例Ki-67阴性患者的中位DFS和OS分别为52.0个月和53.3个月;无论Ki-67阳性或阴性表达,接受SERM或AI治疗患者的DFS和OS均无显著差异。结论 在Ki-67阳性乳腺癌术后辅助化疗中,蒽环类序贯紫杉类方案疗效优于蒽环类方案。在ER阳性接受内分泌治疗的绝经患者中,SERM和AI在不同Ki-67表达者中的疗效相当。     

125I放射性粒子植入联合化疗治疗直肠癌术后辅助放疗后局部复发

目的：评价 CT 引导下125 I 放射性粒子植入术联合 FOLFIRI 方案化疗二线治疗直肠癌术后辅助放疗后局部复发的疗效和安全性。方法34例既往有局部放疗史的直肠癌术后局部复发患者分为2组,对照组仅予 FOLFIRI 方案化疗,研究组予125 I 放射性粒子植入联合 FOLFIRI 方案化疗。术后每2个月参照 RE-CIST 标准评价近期疗效,采用寿命表法计算1、2、3 a 生存率,采用 log rank 法比较亚组生存差异并绘制生存曲线。结果对照组有效率为250%,研究组为1000%（P ＜0001）。中位局部控制时间对照组为4个月,研究组为12个月（P ＜0001）;2组总生存时间分别为19、36个月（P =00168）。结论 CT 引导下125 I放射性粒子植入术联合 FOLFIRI 方案化疗可作为直肠癌术后辅助放疗后局部复发的补救治疗。     

重组人血管内皮抑素联合一线化疗治疗晚期结直肠癌的临床观察

目的对比评价重组人血管内皮抑素(商品名恩度)联合奥沙利铂+亚叶酸钙+5-氟尿嘧啶(FOLFOX4方案)或者伊立替康+亚叶酸钙+5-氟尿嘧啶(FOLFIRI方案)一线治疗进展期结直肠癌(CRC)的疗效和安全性。方法回顾性分析2008年1月至2012年12月间局部晚期不能手术或转移性CRC患者43例,分别接受恩度联合FOLFOX4方案(29例,FOLFOX4组)或FOLFIRI方案(14例,FOLFIRI组)进行一线化疗。3个周期后按照RECIST 1.1标准评价客观疗效,根据NCI CTC 3.0标准评价不良反应,同时观察无进展生存期(PFS)和总生存期(OS)。结果 FOLFOX4组患者中,肿瘤低分化、原发灶未切除以及肝转移比例明显高于FOLFIRI组(均P<0.05)。有40例患者可评价客观疗效,其中FOLFOX4组27例,FOLFIRI组13例。FOLFOX4组患者中,CR 1例,PR 16例,SD 7例,PD 3例,客观缓解率(RR)为63.0%,疾病控制率(DCR)为88.9%;中位PFS为5.6个月,中位OS为15.7个月。FOLFIRI组患者中,PR 5例,SD 6例,PD 2例,RR为38.5%,DCR为84.6%;中位PFS为5.4个月,中位OS为16.5个月。两组患者的客观疗效、中位PFS和中位OS差异均无统计学意义(P>0.05)。两组最常见的不良反应均为消化道反应和骨髓抑制,以1~2级为主。FOLFOX4组患者血小板下降的发生率显著高于FOLFIRI组(P=0.006),FOLFIRI组患者3~4级腹泻的发生率有高于FOLFOX4组的趋向(P=0.057)。结论恩度联合FOLFOX4方案或FOLFIRI方案一线治疗进展期CRC的客观疗效和生存时间差异无统计学意义(P>0.05),不良反应均较轻微但各有侧重,临床上应根据患者实际情况选择用药方案。     

紫杉醇联合FOLFOX4方案治疗晚期胃癌的临床观察

目的观察并比较紫杉醇联合FOLFOX4方案与FOLFOX4方案治疗晚期胃癌的疗效及毒副反应。方法随机将晚期胃癌患者分为两组,A组32例,采用紫杉醇联合FOLFOX4方案化疗;B组31例,采用FOLFOX4方案化疗。每2周重复,28d为1周期,每例患者至少完成2周期以上的化疗。结果A组有效率（CR＋PR）为43.7%,中位疾病进展时间5.87个月,中位生存期9.8个月;B组有效率（CR＋PR）为35.5%,中位疾病进展时间3.9个月,中位生存期8.5个月。两组有效率差异无显著性（P〉0.05）,中位疾病进展时间及中位生存期差异均有显著性（P〈0.05）。两组主要毒副反应为白细胞下降、脱发、肌肉关节痛,两组发生率比较差异具有显著性（P〈0.05）。结论紫杉醇联合FOLFOX4方案治疗晚期胃癌具有良好的疗效和耐受性。     

奥沙利铂或伊立替康联合5-氟尿嘧啶和亚叶酸钙用于不可切除的结直肠癌肝转移术前化疗的比较

目的比较奥沙利铂联合5-氟尿嘧啶和亚叶酸钙(FOLFOX方案)与伊立替康联合5-氟尿嘧啶和亚叶酸钙(FOLFIRI方案)用于不可切除局限于肝转移的结直肠癌术前化疗的疗效和安全性。方法 回顾性分析符合条件的58例结直肠癌患者的临床资料,其中32例应用FOLFOX4或改良FOLFOX6方案,26例应用FOLFIRI方案。中位随访41月,比较两组的化疗客观反应率(response rate,RR),手术根治性(rate of radical,R0)切除率,无进展生存时间(progression-free survival,PFS),总生存时间(overall surviva,OS)和安全性。结果 FOLFOX组的RR为56.3%,FOLFIRI组为42.3%,差异无统计学意义(P=0.429)。FOLFOX组的R0切除率为34.4%,FOLFIRI组为26.9%(P=0.397)。化疗反应率与手术切除率及R0切除率之间存在正相关关系(r=0.840和r=0.671,P<0.001)。FOLFOX组和FOLFIRI组的中位PFS分别为13.5月和11.2月(P=0.533),中位OS分别为21.6月和21.1月(P=0.596)。两组常见的血液学及消化道毒性没有明显区别(P均>0.05),FOLFOX组各级神经病变的发生率(37.5%)要明显高于FOLFIRI组(3.8%,P=0.003)。结论 FOLFOX方案和FOLFIRI方案用于不可切除的结直肠癌肝转移术前化疗,疗效相似,毒性可接受,可作为结直肠癌肝转移术前化疗的选择。     

FOLFOX方案辅助化疗治疗43例根治术后结直肠癌

[目的]分析FOLFOX方案辅助化疗结直肠癌的疗效、疗效预测因素及毒副反应。[方法]43例根治术后病理确诊为结直肠癌的患者行FOLFOX方案辅助化疗,化疗2～12个周期,中位化疗6个周期。以无病生存期（DFS）、总生存期（OS）、毒副反应作为观察指标,采用Kaplan-Meier法绘制生存曲线。Cox多因素回归分析探讨疗效预测因素。[结果]中位随访22个月,中位DFS24.0个月,2年无病生存率46.6%,3年无病生存率23.3%。2年OS93.3%,3年OS69.7%。Cox回归分析显示DSF的预测因素是肿瘤分期、肿瘤部位、化疗周期数。最常见毒副反应为骨髓抑制、胃肠道反应、周围神经毒性。[结论]FOLFOX方案用于结直肠癌辅助化疗疗效较好,毒副反应可以耐受。化疗周期数是影响疗效的可能因素。     

奥沙利铂亚叶酸钙和氟尿嘧啶联合中医药治疗大肠癌术后患者的多中心临床研究

目的评价奥沙利铂＋亚叶酸钙＋氟尿嘧啶（FOLFOX方案）联合中医药治疗Ⅱ～Ⅲ期大肠癌术后患者生存期的影响。方法选取2009年5月至2010年5月间湖南省中医药研究院附属医院（60例）、湖南省肿瘤医院（35例）、湖南省直医院（38例）、邵阳市中医院（33例）和衡阳市中医院（27例）收治的Ⅱ～Ⅲ期大肠癌术后患者193例,采用随机同期对照法分为观察组（99例）和对照组（94例）,两组均接受6个周期FOLFOX方案辅助化疗。观察组采用FOLFOX方案联合中医药治疗,对照组仅采用FOLFOX方案治疗,观察并随访记录两组患者的无病生存时间（DFS）,并统计1、2、3、4、5年生存率。结果观察组患者DFS为36.6个月,对照组为28.2个月（P〈0.05）。观察组患者1、2、3、4、5年生存率分别为99.0%、84.8%、68.7%、66.7%和65.7%,对照组分别为97.9%、74.5%、57.4%、43.6%和42.6%（P〈0.01）;结论大肠癌患者术后采用FOLFOX方案联合中医药综合治疗,可以延长生存时间,提高生存率。     

三氧化二砷改善胃癌患者术后辅助化疗疗效同时减轻骨髓抑制

Objective: The aim of the study was to investigate the prospective study if treatment with arsenic trioxide (As2O3) could enhance disease-free survival as adjuvant post-operative chemotherapy for gastric cancer patients and protect bone marrow from the negative effects of chemotherapy. Methods: 84 adults were randomized into two groups. Patients in treat- ment group were treated with As203 and FOLFOX regimen, the other were administered with FOLFOX regimen only. Results: Four patients were withdrawn in treatment group after 3-4 cycles and the reasons were headache and fidgety (n = 2), ar- rhythmia (n = 1) and AST/ALT elevation (n = 1), while 1 patient in control group after 4 cycles for neutropenia. In the treatment group, the median DFS was 28.34 months (95% CI, 25-33 months). While in control group, the median DFS was 24.50 months (95% CI, 20-30 months). This difference was not statistically significant (chi-square: 2.8885; P value: 0.0892). Pa- tients in the same subgroup of node-positive was 29 in the treatment group and 32 in control group, respectively. The median DFS was 27.87 months (95% CI, 25-31 months) in the treatment group and 24.18 months (95% CI, 19-31 months) in the control group with promising statistical significance (HR 1.89; chi-square: 4.78; P value: 0.0287). The most common grades 3-4 toxicity was leucopenia (n = 11) in control group and the difference was significant (chi-square: 3.9768, P value: 0.046) compared with that in treatment group (n = 4). Conclusion: The combination of arsenic trioxide and FOLFOX regimen has a potential advantage of enhancing disease-free survival in patients with gastric cancer in nodal-positive status as post-opera- tive chemotherapy, and protect bone marrow from the negative effects of chemotherapy.     

贝伐珠单抗联合FOLFOX或FOLFIRI方案治疗转移性结直肠癌的临床研究

目的 观察贝伐珠单抗联合FOLFOX或FOLFIRI方案用于转移性结直肠癌一线及二线治疗的临床疗效和毒副反应。方法 回顾性分析2005年11月至2012年8月接受贝伐珠单抗联合FOLFOX或FOLFIRI方案作为一线及二线治疗的57例转移性结直肠癌患者的临床资料。采用RECIST 1.1版评价疗效,用NCI-CTC 3.0版评价不良反应,用Kaplan-Meier法进行生存分析。结果 57例结直肠癌患者中,19例（33.3％）获PR,28例（49.2％）获SD,有效率（RR）为33.3％,疾病控制率（DCR）为82.5％。贝伐珠单抗联合化疗用于一线与二线治疗患者的RR或DCR差异均无统计学意义（P＞0.05）;贝伐珠单抗联合FOLFOX方案与FOLFIRI方案的RR或DCR差异均无统计学意义（P＞0.05）。57例患者的无进展生存期（PFS）及总生存期（OS）分别为8.83个月及14.80个月。一线与二线治疗及贝伐珠单抗联合FOLFOX方案与FOLFIRI方案的中位PFS或OS差异均无统计学意义（P＞0.05）。主要不良反应包括白细胞减少、血小板减少及恶心呕吐。贝伐珠单抗相关的不良反应主要包括高血压3例,蛋白尿1例,鼻衄2例,均为1～2级,药物可以控制。结论 贝伐珠单抗联合化疗治疗转移性结直肠癌能够提高治疗疗效,不良反应可以耐受。     

Bevacizumab in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in patients with metastatic colorectal cancer who were previously treated with oxaliplatin-containing regimens: a multicenter observational cohort study (TCTG 2nd-BV study)

The efficacy of bevacizumab combined with infusional 5-fluorouracil/leucovorin (5-FU/LV) plus irinotecan (FOLFIRI) as the second-line treatment for metastatic colorectal cancer (mCRC) has not been fully clarified, although bevacizumab combined with infusional 5-FU/LV plus oxaliplatin (FOLFOX) in the second-line setting has demonstrated a survival benefit. We investigated the efficacy of bevacizumab plus FOLFIRI in mCRC patients who failed oxaliplatin-containing regimens without bevacizumab. Patients who received bevacizumab plus FOLFIRI or bevacizumab plus FOLFOX as second-line chemotherapy between July 2007 and March 2008 were registered (trial registration: UMIN000001547). Patient background data and progression-free survival (PFS), overall survival (OS), response, and bevacizumab-related adverse events were prospectively collected every 6?months. A total of 195 patients were enrolled from 26 institutions. Among them, 115 patients received bevacizumab plus FOLFIRI after failure of oxaliplatin and fluoropyrimidine (FOLFIRI+BV after OX/FU group), and 45 patients received bevacizumab plus FOLFOX after failure of irinotecan and fluoropyrimidine (FOLFOX+BV after IRI/FU group). Median PFS was 8.3?months (95% confidence interval [CI], 6.7-9.9) for the FOLFIRI+BV after OX/FU group and 7.8?months (95% CI, 5.8-9.7) for the FOLFOX+BV after IRI/FU group. Median OS was 21.6?months (95% CI, 17.6-25.6) and 16.5?months (95% CI, 11.8-21.2), respectively. Overall response rates were 25 and 29%, respectively. The most common grade ≥3 bevacizumab-related adverse events were hypertension (5.0%) and bleeding (3.8%). FOLFIRI+BV after OX/FU showed comparable efficacy to FOLFOX+BV after IRI/FU.     

Current status of adjuvant therapy for colorectal cancer

Adjuvant therapy with chemotherapy and/or radiation therapy in addition to surgery improves outcome for patients with high-risk carcinomas of the colon or rectum. For colon cancer, fluorouracil (5-FU) combined with leucovorin is a current standard of care that improves long-term survival. A recent European trial (MOSAIC) has documented significant improvement in 3-year disease-free survival when oxaliplatin (Eloxatin) was added to infusional 5-FU and leucovorin in the FOLFOX regimen. Two US cooperative group trials will evaluate the addition of antiangiogenesis therapy with bevacizumab (Avastin) to chemotherapy. A third trial will evaluate FOLFOX, irinotecan (Camptosar) combined with infusional 5-FU and leucovorin (FOLFIRI), and the sequential use of FOLFOX followed by FOLFIRI. In rectal cancer, postoperative 5-FU-based chemotherapy combined with irradiation can improve both local tumor control and survival. The German Rectal Cancer Group has recently reported that preoperative combined-modality therapy is less toxic and more effective in preventing local tumor relapse compared to similar treatment given postoperatively. A coordinated pair of cooperative group clinical trials will evaluate oral capecitabine (Xeloda) as a radiation enhancer in the preoperative setting, and the FOLFOX and FOLFIRI regimens compared to 5-FU and leucovorin following surgery. Predictive and prognostic molecular markers will be studied in these new adjuvant therapy clinical trials for both colon and rectal cancer with the goal of developing future regimens tailored to individual patients. There has been a recent and dramatic increase in the pace of drug development for colorectal cancer which holds promise to further improve curative therapy as part of a multidisciplinary approach in the surgical adjuvant setting.     

伊立替康联合氟尿嘧啶时辰化疗在晚期结直肠癌中的应用

目的　探讨伊立替康联合氟尿嘧啶时辰化疗治疗晚期结直肠癌的疗效和毒副反应。方法　分析我院自２００７年６月至２００８年１２月应用伊立替康联合氟尿嘧啶时辰化疗方案治疗的３２例晚期结直肠癌患者的疗效和毒副反应,并与我院同时期应用ＦＯＬＦＩＲＩ方案化疗的３１例晚期结直肠癌患者进行比较。结果　时辰化疗方案和ＦＯＬＦＩＲＩ方案的总有效率（ＲＲ）、疾病控制率（ＤＣＲ）分别为２１.９％、６５.６％和２５.８％、５８.１％。时辰化疗方案的中位疾病进展时间（ｍＴＴＰ）为６.４个月,中位总生存时间（ｍＯＳ）为９.０个月;ＦＯＬＦＩＲＩ方案的ｍＴＴＰ为５.０个月,ｍＯＳ为７.９个月,两组比较差异均无统计学意义（Ｐ＞０.０５）。两方案常见的毒副反应为恶心呕吐、中性粒细胞减少和腹泻,但多以１～２级为主;３～４级毒副反应在时辰化疗方案中的发生率低于ＦＯＬＦＩＲＩ方案。结论　伊立替康联合氟尿嘧啶时辰化疗方案具有疗效高、毒副作用低等优点,可作为晚期结直肠癌的推荐化疗方案之一。     

Prognostic implication of mucinous histology in colorectal cancer patients treated with adjuvant FOLFOX chemotherapy

Background:

There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear.

Methods:

Stage II and III colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Patients were grouped according to the mucinous content: >50%, mucinous adenocarcinoma (MAC); <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Clinicopathological features and disease-free survival (DFS) were compared.

Results:

Among a total of 521 patients, 27 patients (5.2%) had MAC, 41 patients (7.9%) had AIM, and 453 patients (86.9%) had NMA. Mucinous adenocarcinoma and AIM had higher frequency of proximal location and microsatellite instability, but lower frequency of angiolymphatic invasion. Disease-free survival was significantly worse in the MAC compared with NMA (3-year DFS 57% and 86%, respectively; P<0.001) and AIM (3-year DFS 87%, P=0.01 vs MAC). Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted hazard ratio 7.96, 95% confidence interval 3.76–16.8).

Conclusion:

Adenocarcinoma with intermediated mucinous component and MAC have distinct clinicopathological features compared with NMA. Mucinous adenocarcinoma has an adverse prognostic impact on stage II or III colorectal cancer treated with adjuvant FOLFOX.     

FOLFOX4 versus sequential dose-dense FOLFOX7 followed by FOLFIRI in patients with resectable metastatic colorectal cancer (MIROX): a pragmatic approach to chemotherapy timing with perioperative or postoperative chemotherapy from an open-label,randomized phase III trial

The sequential FOLFOX7–FOLFIRI combination is not superior to FOLFOX4 in colorectal cancer patients with resectable metastases. Patients with synchronous metastases preferably received perioperative chemotherapy, while patients with metachronous metastases were given postoperative chemotherapy in preference. We observed the highest long-term survival rates ever reported in this setting.BackgroundPerioperative FOLFOX4 (oxaliplatin plus 5-fluorouracil/leucovorin) chemotherapy is the current standard in patients with resectable metastases from colorectal cancer (CRC). We aimed to determine whether a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is superior to FOLFOX4. The chemotherapy timing was not imposed, and was perioperative or postoperative.Patients and methodsIn this open-label, phase III trial, patients with resectable or resected metastases were randomly assigned either to 12 cycles of FOLFOX4 (oxaliplatin 85 mg/m²) or 6 cycles of FOLFOX7 (oxaliplatin 130 mg/m²) followed by 6 cycles of FOLFIRI (irinotecan 180 mg/m²). Randomization was done centrally, with stratification by chemotherapy timing, type of local treatment (surgery versus radiofrequency ablation with/without surgery), and Fong's prognostic score. The primary end point was 2-year disease-free survival (DFS).ResultsA total of 284 patients were randomized, 142 in each treatment group. Chemotherapy was perioperative in 168 (59.2%) patients and postoperative in 116 (40.8%) patients. Perioperative chemotherapy was preferentially proposed for synchronous metastases, whereas postoperative chemotherapy was more frequently used for metachronous metastases. Two-year DFS was 48.5% in the FOLFOX4 group and 50.0% in the FOLFOX7–FOLFIRI group. In the multivariable analysis, more than one metastasis [hazard ratio (HR) = 2.15] and synchronous metastases (HR = 1.63) were independent prognostic factors for shorter DFS. Five-year overall survival (OS) rate was 69.5% with FOLFOX4 versus 66.6% with FOLFOX7–FOLFIRI.ConclusionsFOLFOX7–FOLFIRI is not superior to FOLFOX4 in patients with resectable metastatic CRC. Five-year OS rates observed in both groups are the highest ever reported in this setting, possibly reflecting the pragmatic approach to chemotherapy timing.Clinical trials numberNCT00268398.     

贝伐单抗联合FOLFIRI方案一线治疗转移性结直肠癌的临床评价

目的评价贝伐单抗联合FOLFIRI方案一线治疗转移性结直肠癌的疗效和安全性。方法将40例转移性结直肠癌患者随机分为FOLFIRI组和FOLFIRI+贝伐单抗组。FOLFIRI组采用CPT-11(180 mg/m²)+甲酰四氢叶酸(200 mg/m²)+5-Fu(1 000 mg／m²)。FOLFIRI+贝伐单抗组采用贝伐单抗(每2周5 mg/kg)+FOLFIRI方案;两组患者均持续治疗至病情进展或毒性不能耐受。结果40例患者均可评价疗效和不良反应。FOLFIRI组和FOLFIRI+贝伐单抗组的治疗有效率分别为25％(5/20)和60％(12／20)（χ²=5.013,P=0.025),中位无疾病进展时间(DFS)分别为5.1和10.1月(χ²=9.703,P=0.002)。两组患者的1年生存率分别为48％和70%,中位生存时间(OS)分别为11.0月和18.0月,总生存期在两组间差异有统计学意义(χ²=5.852,P=0.016)。两组的主要不良反应为迟发性腹泻和中性粒细胞减少,FOLFIRI+贝伐单抗组增加的不良反应主要有高血压、出血、蛋白尿和心脏毒性,但患者可以耐受。结论FOLFIRI方案化疗联用贝伐单抗提高了晚期结直肠癌患者治疗的有效率,并延长了DFS及OS,不良反应患者可以耐受。