XELOX与FOLFOX6方案一线治疗晚期结直肠癌的近期疗效及不良反应比较

目的:比较卡培他滨(希罗达)联合奥沙利铂(XELOX)方案与亚叶酸钙、5-氟尿嘧啶(5-FU)联合奥沙利铂(FOLFOX6)方案一线治疗晚期转移性结、直肠癌的疗效和不良反应.方法: 将62例晚期结、直肠癌患者随机分为两组,XELOX方案组(n=31):卡培他滨(capecitabine,Xeloda)1000mg/m2,2次/d,口服,第1天至第14天;奥沙利铂(oxaliplatin)130mg/m2,静脉滴注,持续3h,第1天;21天为1周期.FOLFOX6方案组(n=31):亚叶酸钙(CF)200mg/m2,静脉滴注,第1天,5-FU前;5-FU 400mg/m2,静脉推注,第1天,2400mg/m2,静脉持续滴注46h;奥沙利铂100mg/m2,静脉滴注,持续3h,第1天;14天为1周期. 结果: XELOX组缓解率(RR)为48.4%,中位肿瘤进展时间(TTP)6.8个月;FOLFOX6组RR为51.6%,TTP为7.1个月;两组比较各项指标差异无统计学意义(P＞0.05).不良反应中XELOX组手足综合征发生率高于FOLFOX组,Ⅲ、Ⅳ度中性粒细胞减少发生率低于FOLFOX6组.结论: XELOX 方案一线治疗晚期结、直肠癌有确切疗效,不良反应能耐受,与FOLFOX6方案相当,但XELOX方案用药更为方便,安全性更好.     

XELOX与FOLFOX6应用于晚期结直肠癌治疗的临床观察

目的探讨卡培他滨+奥沙利铂(XELOX)化疗方案与亚叶酸钙/5-氟脲嘧啶+奥沙利铂(FOLFOX6)化疗方案治疗晚期结直肠癌的近期疗效、不良反应及远期生存率的影响。方法选取106例晚期结直肠癌患者为研究对象,其中接受XELOX化疗方案者57例,接受FOLFOX6方案者49例。对比2组治疗总疗效、不良反应发生情况以及生存率。结果治疗后,XELOX组总有效率为56.14%,FOLFOX6组总有效率为53.06%,2组差异无统计学意义(P>0.05)。XELOX化疗组手足综合征发生率为14.04%,明显高于FOLFOX6化疗组发生率2.04%,差异有统计学意义(P<0.05),但其程度较轻,主要以Ⅰ~Ⅱ度为主;FOLFOX6化疗组神经毒性发生率为22.45%,明显高于XELOX化疗组发生率5.26%(P<0.05),程度较轻,主要以Ⅰ~Ⅱ度为主;2组在白细胞减少、恶心、呕吐、口腔炎、脱发等发生率上比较,差异无统计学意义(P>0.05)。XELOX组疾病无进展生存时间中位数为15个月,FOLFOX6组17个月;XELOX化疗组1年生存率为85.96%,高于FOLFOX6化疗组1年生存率83.67%,但差异无统计学意义(P>0.05)。结论 XELOX与FOLFOX6化疗方案治疗晚期结直肠癌的疗效相当,但XELOX化疗方案用药更为安全方便。     

FOLFOX4方案与XELOX方案治疗转移性结直肠癌的疗效与不良反应分析

目的 对比分析FOLFOX4和XELOX方案治疗的转移性结直肠癌的疗效和不良反应.方法 选择转移性结直肠癌患者72例,按照姑息化疗方案的不同分为XELOX组38例和FOLFOX4组34例.XELOX组患者口服卡培他滨1000 mg/m2,早晚各服1次,连续服用14 d,奥沙利铂130 mg/m2静脉点滴,第1d,21 d为一个治疗周期.FOLFOX4组患者奥沙利铂85 mg/m2静脉滴注2h,第1d,亚叶酸钙200 mg/m2静脉滴注2h,第1～2d,5-氟尿嘧啶400 mg/m2快速静脉滴注后再用600 mg/m2静脉滴注22 h,第1～2 d,14 d为一个治疗周期.结果 XELOX组患者5年无病生存率为55.3％,FOLFOX4组患者5年无病生存率为45.2％,差异无统计学意义(x2=1.531,P=0.216).XELOX组患者有效率为52.6％,FOLFOX4组患者有效率为47.1％,两组有效率比较无显著差异(P＞0.05).XELOX组患者白细胞减少发生率为47.3％,血小板减少发生率为15.8％,显著低于FOLFOX4组(64.7％和32.4％),差异有统计学意义(P＜0.05);XELOX组患者手足综合征的发生率为39.5％,显著高于FOLFOX组(8.8％),差异具有统计学意义(P＜0.05).结论 XELOX方案治疗转移性结直肠癌的疗效与FOLFOX4相当,但是安全性较高.     

XELOX方案治疗晚期结直肠癌临床观察

目的比较卡培他滨(希罗达)联合奥沙利铂(XELOX)方案与亚叶酸钙、氟尿嘧啶(5-Fu)联合奥沙利铂(FOLFOX4)方案一线治疗晚期转移性结直肠癌的疗效和不良反应。方法将56例晚期结直肠癌患者随机分为两组,XELOX方案组(28例):卡培他滨(capecitabine,Xeloda)1000mg/m2,Bid,口服,d1~14;奥沙利铂(oxaliplatin)130mg/m2,静脉滴注,持续2h,d1;21 d为1周期。FOLFOX4方案组(28例):奥沙利铂85 mg/m2,静脉点滴2 h,d1;醛氢叶酸200 mg/m2,静脉点滴2 h,d1、2;氟尿嘧啶400 mg/m2,莫非氏管静脉推注d1、2;氟尿嘧啶600 mg/m2,静脉持续滴注(化疗泵),持续22 h,d1、2,14 d为1周期。结果 XELOX组总有效率(RR)50.0%,中位肿瘤进展时间(TTP)7.0个月;FOLFOX4组RR为46.4%,TTP为6.8个月;两组比较各项指标差异无显著性(P>0.05)。不良反应中XELOX组手足综合征发生率高于FOLFOX4组,Ⅲ、Ⅳ度中性粒细胞减少发生率低于FOLFOX4组。结论 XELOX方案一线治疗晚期结直肠癌有确切疗效,不良反应可耐受,与FOL-FOX4方案相当,但XELOX方案用药更为方便,安全性更好。     

奥沙利铂联合替吉奥方案与 XELOX 方案在晚期结直肠癌治疗中的疗效及毒副作用对比

目的：探讨奥沙利铂联合替吉奥方案与XELOX方案（奥沙利铂联合卡培他滨）治疗晚期结直肠癌的疗效及毒副作用。方法将168例晚期结直肠癌患者随机分为2组,对照组患者采用XELOX方案治疗,观察组患者采用奥沙利铂联合替吉奥方案进行治疗。观察对比2组患者化疗后的疗效情况和毒副作用发生情况。结果观察组化疗总有效率（CR＋PR）为48．84％,与对照组的51．22％比较,差异无统计学意义（P＞0．05）。2组患者化疗后的疾病控制率（DCR）比较差异不明显（P＞0．05）。化疗后,2组患者骨髓抑制、胃肠道反应、口腔黏膜病变、神经毒性和肾损伤的发生率比较差异不明显（P＞0．05）。观察组患者化疗后手足综合征和肝损伤的发生率均明显高于对照组（P＜0．05）。结论奥沙利铂联合替吉奥方案与XELOX方案化疗均可有效治疗晚期结直肠癌,且XELOX方案的不良反应更小,安全性更高,有利于临床治疗。     

XELOX方案与FOLFOX4方案治疗转移性结直肠癌的临床观察

目的:观察两种常用化疗方案卡培他滨联合奥沙利铂方案(XELOX)与5-氟尿嘧啶/亚叶酸钙联合奥沙利铂方案(FOLFOX4)治疗转移性结直肠癌的临床疗效及不良反应.方法:48例晚期结直肠癌患者随机分成两组,XELOX组与FOLFOX4组.XELOX组25例,予卡培他滨联合奥沙利铂方案化疗,卡培他滨1000mg/m2,口服,2次/日,第1-14天;奥沙利铂130mg/m2,静脉点滴,第1天;21天1周期.FOLFOX4组23例,予5-氟尿嘧啶,亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85mg/m2,静脉点滴,第1天;亚叶酸钙200mg/m2,静滴2小时后予5-氟尿嘧啶400mg/m2,推注,后续600mg/m2持续静滴22小时,第1、2天;每2周重复,4周为1周期.两组均治疗2周期以上.按WHO标准评价客观疗效和不良反应.结果:48例均可评价疗效,XELOX组有效率48.0%(CR 2,PR 10),中位TTP 7.1个月,MST 13.8个月,FOLFOX4组有效率47.8%(CR 2,PR 9),中位TTP 7.3个月,MST 14.0个月.两组近期有效率无明显统计学差异.不良反应比较,手足综合征以XELOX组显著(P<0.05),Ⅲ-Ⅳ级恶心呕吐发生率FOLFOX4组高(P<0.05),余不良反应除腹泻外发生率以FOLFOX4组稍高,但无统计学意义.结论:XELOX方案与FOLFOX4方案治疗晚期结直肠癌疗效确切,不良反应能耐受.两组近期疗效相似,不良反应XELOX组更低.     

XELOX方案与FOLFOX4方案治疗转移性结直肠癌的临床观察

目的：观察两种常用化疗方案卡培他滨联合奥沙利铂方案（XELOX）与5-氟尿嘧啶/亚叶酸钙联合奥沙利铂方案（FOLFOX4）治疗转移性结直肠癌的临床疗效及不良反应。方法：48例晚期结直肠癌患者随机分成两组,XELOX组与FOLFOX4组。XELOX组25例,予卡培他滨联合奥沙利铂方案化疗,卡培他滨1000mg／m^2,口服,2次／日,第1—14天;奥沙利铂130mg／m^2,静脉点滴,第1天;21天1周期。FOLFOX4组23例,予5-氟尿嘧啶,亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85mg／m^2,静脉点滴,第1天;亚叶酸钙200mg／m^2,静滴2小时后予5-氟尿嘧啶400mg／m^2,推注,后续600mg／m^2持续静滴22小时,第1、2天;每2周重复,4周为1周期。两组均治疗2周期以上。按WHO标准评价客观疗效和不良反应。结果：48例均可评价疗效,XELOX组有效率48．0％（CR2,PR10）,中位TTP 7．1个月,MST 13．8个月,FOLFOX4组有效率47．8％（CR2,PR9）,中位TTP 7．3个月,MST 14．0个月。两组近期有效率无明显统计学差异。不良反应比较,手足综合征以XELOX组显著（P〈0．05）,Ⅲ-Ⅳ级恶心呕吐发生率FOLFOX4组高（P〈0．05）,余不良反应除腹泻外发生率以FOLFOX4组稍高,但无统计学意义。结论：XELOX方案与FOLFOX4方案治疗晚期结直肠癌疗效确切,不良反应能耐受。两组近期疗效相似,不良反应XELOX组更低。     

DX方案与XELOX方案一线治疗晚期胃癌疗效比较

目的 观察DX方案（多西紫杉醇联合卡培他滨）与XELOX方案（草酸铂联合卡培他滨）治疗晚期胃癌的客观疗效和毒性反应。方法DX方案组21例晚期胃癌患者接受多西紫杉醇75mg／m^2d1卡培他滨每日1700mg／m^2,分2次口服,dl—14,21d为1周期,疗程2—6周期。XELOX方案组20例晚期胃癌患者接受奥沙利铂130mg／m^2dl,卡培他滨每日1700mg／m^2,分2次口服,dl—d14,21d为1周期,疗程2—6周期。结果DX方案组总有效率为52．4％常见的毒性反应为中性粒细胞减少性发热、脱发、腹泻及口腔黏膜炎发生率较高;XELOX方案组总有效率为50．0％,常见的毒性反应为手足综合征和周围神经毒性反应等。结论DX方案和XELOX方案均为治疗进展期胃癌较好的方案,其中XELOX方案副反应较低可提高患者的生存质量,毒副作用能耐受,更适合老年体弱病人。     

XELOX双周方案治疗晚期胃肠癌的近期疗效

目的 观察奥沙利铂联合卡培他滨(XELOX)双周方案治疗晚期胃、结直肠癌的临床疗效和不良反应。方法 46例晚期胃、结直肠癌患者应用奥沙利铂85mg/m2,静滴2h,d1;卡培他滨 （900～1000）mg/m2,一日分两次,口服,d1～10;14d为1周期,4周期评价疗效。结果 46例均可评价疗效,CR 4例,PR 24例,RR 65.2％;不良反应主要为I～Ⅱ度血液学毒性,恶心、呕吐,末梢神经异常及手足综合征。结论 奥沙利铂联合卡培他滨(XELOX)双周方案治疗晚期胃、结直肠癌疗效确切,耐受性好,值得临床推广应用。     

XELOX方案与OLF方案治疗晚期结直肠癌的临床观察

目的 研究Xeloda(卡培他滨),与氟尿嘧啶/亚叶酸钙持续静脉滴注分别与奥沙利铂(L-OHP)联合治疗晚期结直肠癌的疗效,并进行毒性对照研究以找到一种临床上更安全有效的方案.方法 52例病人随机分两组,A组27例,予Xeloda 1000 mg/m2口服2次/日,连用14天,奥沙利铂135 mg/m2静滴d1,21天为一周期.B组为25例,CF 0.1静滴d1-5,5-Fu 500 mg/(m2·d),持续静脉滴注120小时,奥沙利铂135 mg/m2静滴d1,21天为一周期.结果 A组有效率51.8﹪,B组为48﹪,无明显差异,主要毒副反应,血液毒性,胃肠道反应,XELOX均低于OLF方案,有显著差异.结论 Xeloda联合草酸铂治疗晚期结直肠癌疗效高、且毒副反应低,依从性好,值得临床一线应用.     

Capecitabine plus oxaliplatin (XELOX) versus 5‐fluorouracil/leucovorin plus oxaliplatin (FOLFOX‐6) as first‐line treatment for metastatic colorectal cancer

A regimen consisting of 5‐fluorouracil/leucovorin plus oxaliplatin (FOLFOX‐6) is widely used in France in the first‐line treatment of metastatic colorectal cancer (MCRC). The aim of our study was to demonstrate the non‐inferiority of capecitabine plus oxaliplatin (XELOX) versus FOLFOX‐6 for this indication. Patients were randomly assigned to receive XELOX or FOLFOX‐6 for 6 months. The primary endpoint was overall response rate (ORR) in the per‐protocol (PP) population; however, progression‐free and overall survival (OS), time to response and response duration were also assessed. A total of 306 patients were enrolled (XELOX n = 156; FOLFOX‐6 n = 150). ORR was 42 and 46% with XELOX and FOLFOX‐6, respectively, in the PP population. The difference between groups was 4.7%; the upper limit of the unilateral 95% confidence interval (14.4%) was below the non‐inferiority margin of 15%. In the intent‐to‐treat population, median progression‐free survival was 8.8 months with XELOX and 9.3 months with FOLFOX‐6, and median OS was 19.9 and 20.5 months, respectively. XELOX patients had significantly more grade 3/4 thrombocytopenia (12% vs. 5%) and diarrhoea (14% vs. 7%), but significantly less grade 3/4 neutropenia (5% vs. 47%), febrile neutropenia (0% vs. 6%) and neuropathy (11% vs. 26%) than FOLFOX‐6 patients. We conclude that XELOX is non‐inferior in terms of efficacy to FOLFOX‐6 in the first‐line treatment of MCRC, but has a different toxicity profile.     

XELOX (capecitabine plus oxaliplatin) as first-line treatment for elderly patients over 70 years of age with advanced colorectal cancer

The purpose of this phase II trial was to determine the efficacy and safety of the XELOX (capecitabine/oxaliplatin) regimen as first-line therapy in the elderly patients with metastatic colorectal cancer (MCRC). A total of 50 patients with MCRC aged > or = 70 years received oxaliplatin 130 mg m(-2) on day 1 followed by oral capecitabine 1000 mg m(-2) twice daily on days 1-14 every 3 weeks. Patients with creatinine clearance 30-50 ml min(-1) received a reduced dose of capecitabine (750 mg m(-2) twice daily). By intent-to-treat analysis, the overall response rate was 36% (95% CI, 28-49%), with three (6%) complete and 15 (30%) partial responses. In total, 18 patients (36%) had stable disease and 14 (28%) progressed. The median times to disease progression and overall survival were 5.8 months (95% CI, 3.9-7.8 months) and 13.2 months (95% CI, 7.6-16.9 months), respectively. Capecitabine was well tolerated: grade 3/4 adverse events were observed in 14 (28%) patients: 11 (22%) diarrhoea, eight (16%) asthenia, seven (14%) nausea/vomiting, three (6%) neutropenia, three (6%) thrombocytopenia, and two (4%) hand-foot syndrome. There was one treatment-related death from diarrhoea and sepsis. In conclusion, XELOX is well tolerated in elderly patients, with respectable efficacy and a meaningful clinical benefit response. Given its ease of administration compared with combinations of oxaliplatin with 5-FU/LV, it represents a good therapeutic option in the elderly.     

奥沙利铂联合卡培他滨治疗转移性胃腺癌的临床研究

目的：观察奥沙利铂联合卡培他滨（XELOX）方案一线治疗转移性胃癌的疗效及安全性。方法：2004年1月-2007年6月西安交通大学医学院第一附属医院肿瘤外科收治的、经组织学证实的转移性胃腺癌患者54例,接受XELOX方案化疗,奥沙利铂130 mg/m2,静脉滴注4h,第1天;卡培他滨1000 mg/m2,口服2次/天,第1-14天,每3周重复一次,每2周期后进行疗效评估。结果：54例接受XELOX方案一线治疗的患者均可评价疗效,CR 4例,PR 24例,SD 18例,PD 8例,总有效率为51.8%,临床获益率为85.1%,中位肿瘤进展时间6.0月,中位生存时间12.1月,1年生存率35.1%;XELOX方案治疗发生Ⅲ-Ⅳ级不良反应,其中神经毒性、血液学毒性和消化系统毒性各4例,手足综合征5例。结论：XELOX方案作为一线治疗晚期转移性胃癌疗效肯定,安全性高,不良反应轻,患者耐受性好。     

Systemic therapy for metastatic colorectal cancer: current questions

A proliferation of new cytotoxic and biologic agents has led to improved survival in patients with metastatic colorectal cancer (mCRC). The ability of surgery to increase long-term survival in patients with liver and/or lung metastases also has been firmly established. It has become increasingly difficult as the numbers and types of treatment options have expanded to identify optimal drug combinations, sequences, and duration and the best way to integrate systemic chemotherapy with potentially curative surgery for metastatic lesions. For this review, the authors examined how recent clinical trials have addressed some pertinent questions regarding the use of systemic chemotherapy and biologic agents in patients with mCRC.     

奥沙利铂联合卡培他滨治疗转移性胃腺癌的临床研究

目的:观察奥沙利铂联合卡培他滨(XELOX)方案一线治疗转移性胃癌的疗效及安全性。方法:2004年1月-2007年6月西安交通大学医学院第一附属医院肿瘤外科收治的、经组织学证实的转移性胃腺癌患者54例,接受XELOX方案化疗,奥沙利铂130 mg/m2,静脉滴注4h,第1天;卡培他滨1000 mg/m2,口服2次/天,第1-14天,每3周重复一次,每2周期后进行疗效评估。结果:54例接受XELOX方案一线治疗的患者均可评价疗效,CR 4例,PR 24例,SD 18例,PD 8例,总有效率为51.8%,临床获益率为85.1%,中位肿瘤进展时间6.0月,中位生存时间12.1月,1年生存率35.1%;XELOX方案治疗发生Ⅲ-Ⅳ级不良反应,其中神经毒性、血液学毒性和消化系统毒性各4例,手足综合征5例。结论:XELOX方案作为一线治疗晚期转移性胃癌疗效肯定,安全性高,不良反应轻,患者耐受性好。     

XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results

Background:

We report updated overall survival (OS) data from study NO16966, which compared capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX4) as first-line therapy in metastatic colorectal cancer.

Methods:

NO16966 was a randomised, two-arm, non-inferiority, phase III comparison of XELOX vs FOLFOX4, which was subsequently amended to a 2 × 2 factorial design with further randomisation to bevacizumab or placebo. A planned follow-up exploratory analysis of OS was performed.

Results:

The intent-to-treat (ITT) population comprised 2034 patients (two-arm portion, n=634; 2 × 2 factorial portion, n=1400). For the whole NO16966 study population, median OS was 19.8 months in the pooled XELOX/XELOX-placebo/XELOX-bevacizumab arms vs 19.5 months in the pooled FOLFOX4/FOLFOX4-placebo/FOLFOX4-bevacizumab arms (hazard ratio 0.95 (97.5% CI 0.85–1.06)). In the pooled XELOX/XELOX-placebo arms, median OS was 19.0 vs 18.9 months in the pooled FOLFOX4/FOLFOX4-placebo arms (hazard ratio 0.95 (97.5% CI 0.83–1.09)). FOLFOX4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhoea and grade 3 hand-foot syndrome than FOLFOX4.

Conclusion:

Updated survival data from study NO16966 show that XELOX is similar to FOLFOX4, confirming the primary analysis of progression-free survival. XELOX can be considered as a routine first-line treatment option for patients with metastatic colorectal cancer.     

A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients.

BACKGROUND: Dysregulation of the epidermal growth factor receptor (HER1/EGFR) has been reported in colorectal cancer (CRC). Erlotinib is a potent inhibitor of HER1/EGFR-mediated signaling. This trial of patients with metastatic CRC (MCRC) examined the safety, maximum tolerated dose (MTD) and pharmacokinetics (PK) of erlotinib in combination with capecitabine and oxaliplatin (XELOX), a regimen with established efficacy. PATIENTS AND METHODS: Patients previously untreated or treated with one line of 5-fluorouracil and/or irinotecan received escalating oral doses of erlotinib (daily), capecitabine (days 1-14) and i.v. oxaliplatin (day 1 of a 21-day cycle). RESULTS: The first six patients in cohort 1 (erlotinib 100 mg/day, capecitabine 825 mg/m(2) twice daily, oxaliplatin 130 mg/m(2)) had no dose-limiting toxicities (DLTs). In cohort 2 (capecitabine increased to 1000 mg/m(2) twice daily), two of six patients had DLTs. When cohort 2 was expanded to 11 patients two further DLTs occurred, exceeding the definition of MTD. Cohort 1 was expanded to 12 patients, and no DLTs occurred. The most common adverse events (AEs) were diarrhea and rash. There was a trend for reduced capecitabine concentrations in the presence of erlotinib. While this was not statistically significant, the possibility of an interaction affecting capecitabine PK cannot be excluded. Antitumor activity was observed in both cohorts (one complete and four partial responses, and stable disease in 11 patients). CONCLUSION: The MTD for this combination in MCRC is capecitabine 825 mg/m(2) twice daily days 1-14, oxaliplatin 130 mg/m(2) day 1 and erlotinib 100 mg/day of a 21-day cycle. The combination was well tolerated at the MTD, with no unexpected AEs. The use of this combination in MCRC warrants further investigation.     

Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis

Background:

A dose-finding study was performed to evaluate the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and the recommended dose (RD) of escalating the doses of capecitabine and fixed doses of irinotecan and oxaliplatin on a biweekly schedule for metastatic colorectal cancer patients (mCRC). A pharmacogenomic analysis was performed to investigate the association between SNPs and treatment outcome.

Methods:

Eighty-seven chemotherapy-naïve mCRC patients were recruited through a two-step study design; 27 were included in the dose-finding study and 60 in the pharmacogenomic analysis. Oxaliplatin (85 mg m^-2) and CPT-11 (150 mg m^-2), both on day 1, and capecitabine doses ranging from 850 to 1500 mg m^-2 bid on days 1–7 were explored. Peripheral blood samples were used to genotype 13 SNPs in 10 genes related to drug metabolism or efficacy. Univariate and multivariate Cox analysis was performed to examine associations between SNPs, ORR and PFS.

Results:

The capecitabine RD was 1000 mg m⁻² bid. Diarrhoea and neutropenia were the DLTs. After a median follow-up of 52.5 months, the median PFS and OS were 12 (95% CI; 10.6–13.4) and 27 months (95% CI; 17.2–36.8), respectively.The GSTP1-G genotype, the Köhne low-risk category and use of a consolidation approach strongly correlated with decreased risk of progression. Patients with all favourable variables showed a median PFS of 42 months vs 3.4 months in the group with all adverse factors. A superior clinical response was obtained in patients with one GSTP1-G allele as compared with GSTP1-AA carriers (P=0.004).

Conclusion:

First-line therapy with oxaliplatin, irinotecan and capecitabine is efficient and well-tolerated. The GSTP1 polymorphism A>G status was significantly associated with ORR and PFS in mCRC treated with this triplet therapy.     

Molecular markers of response and toxicity to FOLFOX chemotherapy in metastatic colorectal cancer

Background:

To investigate three genetic alterations (TP53 mutation, Kras mutation and microsatellite instability (MSI)) and three polymorphisms (methylene tetrahydrofolate reductase (MTHFR) C677T, excision repair cross complementing group 1 (ERCC1)-118 and X-ray repair cross complementing group 1 (XRCC1)-399) for their ability to predict response, survival and toxicity to FOLFOX first line chemotherapy in the treatment of metastatic colorectal cancer (mCRC).

Methods:

Tumour tissues from 118 mCRC patients who underwent FOLFOX treatment from three successive phase II trials were evaluated for mutations in TP53 (exons 5–8) and Kras (codons 12 and 13) and for MSI using PCR-based analysis. Genotyping for common single nucleotide polymorphisms in the MTHFR (codon 677), ERCC1 (codon 118) and XRCC1 (codon 399) genes was also carried out using PCR techniques. These genetic markers were correlated with clinical response, survival and toxicity to treatment.

Results:

Patients with the T allele of ERCC1-118 showed significantly worse progression-free survival in univariate analysis (HR=2.62; 95% CI=1.14–6.02; P=0.02). None of the genetic alterations or polymorphisms showed significant association with clinical response to FOLFOX. The MTHFR, ERCC1 and XRCC1 polymorphisms showed no associations with overall haematological, gastrointestinal or neurological toxicity to FOLFOX, although MTHFR 677 TT genotype patients showed a significantly higher incidence of grade 3 or 4 diarrhoea (26%) compared with CC or CT genotype patients (6%, P=0.02).

Conclusions:

The ERCC1-118 and MTHFR C677T polymorphisms were associated with progression and severe diarrhoea, respectively, after FOLFOX treatment in mCRC. Although our findings require confirmation in large prospective studies, they reinforce the concept that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes.