FOLFOX6方案治疗结直肠癌肝转移患者的疗效观察

背景与目的:FOLFOX6方案应用于晚期结直肠癌已有一段时间,但尚未见系统评价FOLFOX6方案临床研究的报道,本研究观察FOLFOX6方案治疗结直肠癌肝转移患者的疗效及不良反应,以评价该方案在中国应用的可行性和临床推广价值.方法:91例结直肠癌肝转移患者采用FOLFOX6方案化疗,即草酸铂100 mg/m2加入5%葡萄糖溶液250 ml中静滴2 h,d1;甲酰四氢叶酸(leucovorin,CF)400 mg/m2加入5%葡萄糖溶液250 ml中静滴2 h,d1,接着用氟尿嘧啶(5-fluorouracil,5-FU)400 mg/m2静脉推注,继以5-FU 2.4 g/m2持续静脉滴注46 h.应用CT、MRI评价每例患者的不良反应及疗效.用x2检验分析两组间有效率的差异,Kaplan-Meier法计算中位生存时间,log-rank法比较生存差异.结果:全组患者CR 4例,PR 33例,SD 19例,PD 35例,有效率40.7%,既往未接受其它治疗(第一组,60例)与既往接受过其它治疗(第二组,31例)的患者有效率差异无显著性(P＞0.05);中位生存17个月,第一组中位生存20个月,第二组中位生存12个月;疾病进展时间(time to progress,TTP)7个月,第一组TTP为9个月,第二组TTP为6个月.主要不良反应为周围神经炎、消化道反应、骨髓抑制等,多为Ⅰ～Ⅱ级,未见Ⅳ级不良反应发生,在用药休息期间或作相应的治疗后均可恢复.结论:FOLFOX6方案作为结直肠癌肝转移的治疗方案,疗效好,且不良反应较轻,是治疗结直肠癌肝转移较为理想的化疗方案.     

mEOF方案与mFOLFOX6方案治疗晚期胃癌的疗效比较

目的:观察和比较mEOF方案（表阿霉素+奥沙利铂+5-氟尿嘧啶）与mFOLFOX6方案（奥沙利铂+ 5-氟尿嘧啶+亚叶酸钙）治疗晚期胃癌的临床疗效、毒副反应、平均住院时间及花费。方法:回顾性分析38例接受mEOF（16例）和mFOLFOX6（22例）方案化疗的晚期胃癌患者,每2个化疗周期后采用RECIST 1.1标准进行疗效评价,每个化疗周期根据NCI-CTC 3.0标准记录毒副反应,每个化疗周期的住院时间及花费从本院的医疗系统（HIS）中采集。结果:mEOF组CR 0例,PR 1例,SD 9例,PD 6例,RR为6.3%,DCR为62.5％,中位PFS为2.2个月;mFOLFOX6组CR 0例,PR 2例,SD 13例,PD 4例,RR为10.5%,DCR为78.9%,中位PFS为5.2个月,两组疗效差异无统计学意义;在对患者的生活质量影响上,mFOLFOX6方案能更好的改善患者的生活质量（P=0.014）;主要毒副反应为骨髓抑制、胃肠道反应,以Ⅰ/Ⅱ度为主,其中,mFOLFOX6组白细胞减少发生率显著高于mEOF组（P=0.009）;mEOF组血小板减少发生率显著高于mFOLFOX6组（P=0.019）。在住院时间及花费方面,mEOF组平均住院时间及费用都明显低于mFOLFOX6组（P=0.00）。结论:mEOF方案和mFOLFOX6方案治疗晚期胃癌疗效相近,毒副反应可耐受,mFOLFOX6方案在改善患者的生活质量方面有优势,mEOF组平均住院时间及费用低于mFOLFOX6组。     

FOLFOX方案化疗对结直肠癌患者免疫细胞数的影响

背景与目的：化疗在杀伤肿瘤的同时,也损害了机体的正常免疫。很多文献曾报道晚期肠癌的化疗,常使细胞免疫功能抑制加重。本研究探讨FOLFOX方案即奥沙利铂联合亚叶酸钙及氟尿嘧啶联合化疗对结直肠癌患者免疫细胞数的影响及与健康人的差异。方法：80例结直肠癌患者行FOLFOX方案化疗（奥沙利铂85mg/m2,静脉滴注,第1天;亚叶酸钙200mg/m2,静脉滴注,第1天;氟尿嘧啶400mg/m2,第1天,2400mg/m2,持续静脉滴注46h）,2周1次,2次为1个疗程,采用流式细胞仪测定化疗前及化疗后2周、4周外周血T淋巴细胞亚群和NK细胞的活性,比较化疗前后的变化,同时根据临床分期进行亚组分析比较,以健康人作对照分析。结果：本组结直肠癌患者第1天、第2周及第4周外周血CD3＋、CD4＋、CD8＋、CD4＋/CD8＋及NK细胞活性比较均无显著下降（P〉0.05）,但患者外周血CD3＋、CD4＋、NK细胞数量及CD4＋/CD8＋比值与健康人相比下降,而CD8＋细胞比例显著升高,差异有显著性（P〈0.05）,提示免疫功能较健康人下降,而且外周血T淋巴细胞亚群和NK细胞数量的改变与结直肠癌临床病理分期有关,分期越晚,CD3＋、CD4＋及NK细胞数量CD4＋/CD8＋细胞比值越低,CD8＋细胞比例越高;Ⅰ、Ⅱ期结直肠癌患者与Ⅲ、Ⅳ期患者之间差异有显著性（P〈0.05）。结论：FOLFOX方案治疗结直肠癌疗效肯定,可改善患者生存质量,而且对机体免疫力影响小。检测淋巴细胞亚群对判断患者的免疫功能、预测肿瘤患者的预后以及指导临床是否需要应用免疫增强剂均有重要意义。     

小牛脾提取物联合FOLFOX方案治疗晚期结直肠癌的临床观察

目的评价小牛脾提取物联合FOLFOX方案治疗晚期结直肠癌的疗效与安全性。方法小牛脾取物10 ml+5%葡萄糖注射液250 ml静滴,奥沙利铂130 mg/m2第1天,亚叶酸钙200mg/m2第1～天5,5-氟尿嘧啶300/m2第1～5天,21 d为1个周期。结果本组有效率(CR+PR)53.1%,不良反应较对照组轻。结论小牛脾提取物联合FOLFOX方案治疗中晚期结直肠癌疗效较高,不良反应轻。     

FOLFOX方案对转移性结直肠癌患者免疫力的影响

目的:观察FOLFOX方案以奥沙利铂联合亚叶酸钙及5氟脲嘧啶化疗对转移性结直肠癌患者细胞免疫的影响。方法:40例晚期结直肠癌患者,行奥沙利铂130mg/m2,静脉滴注,第1天,亚叶酸钙200mg/m2,静脉滴注,第1~5天,5氟脲嘧啶500mg/m2,静脉滴注,第1~5天。3周为1周期。分别于化疗第1天,第7天及第14天采血查细胞免疫。结果:本组患者第1天,与第7天及第14天细胞免疫CD3 、CD4 、CD8 、CD4 /CD8 及NK细胞活性比较,均P>0.05。结论:FOLFOX方案治疗转移性结直肠癌效果肯定,可改善患者生存质量,对机体免疫力影响小。     

ＦＯＬＦＯＸ６方案联合腹部内生场热疗治疗晚期大肠癌的临床研究

目的　评价ＦＯＬＦＯＸ６方案联合腹部内生场热疗治疗晚期大肠癌的疗效和不良反应。方法　对照组３９例采用ＦＯＬＦＯＸ６方案：奥沙利铂１００ｍｇ／ｍ２静滴２小时,第１天;亚叶酸钙（ＣＦ）２００ｍｇ／ｍ２静滴２小时,第１天;氟尿嘧啶（５-ＦＵ）４００ｍｇ／ｍ２静推,第１天,然后总量２４００ｍｇ／ｍ２持续静滴４６小时;每２周重复１次。试验组３９例采用ＦＯＬＦＯＸ６方案化疗的同时（剂量和方法同对照组）,每周期第１天（５-ＦＵ静滴后１小时）、第８天分别进行腹部内生场热疗１小时。４周期治疗结束后评价疗效和毒副反应。结果　试验组有效率（ＣＲ＋ＰＲ）为５６４１％,中位肿瘤进展时间（ＴＴＰ）为９.５个月;对照组有效率为４１.０３％,中位ＴＴＰ为８.６个月,试验组略优于对照组,但两组差异无统计学意义（Ｐ值分别为０.１７４和０.８１２）。试验组神经系统毒性较对照组明显减轻,尤其是肢端感觉异常及面部感觉异常,两组差异有统计学意义（Ｐ值分别为０.０２３和０.０３９）。结论　ＦＯＬＦＯＸ６方案联合腹部内生场热疗治疗晚期大肠癌的疗效好,毒副作用少。     

艾迪注射液联合FOLFOX4方案治疗结肠癌临床观察

目的评价艾迪注射液联合FOLFOX4方案治疗结肠癌的临床疗效。方法患者随机分两组,A组采用单纯FOLFOX4方案（奥沙利铂、亚叶酸钙、氟尿嘧啶）治疗（49例）,B组采用国产中药艾迪注射液联合FOLFOX4方案（45例）,进行比较分析。结果艾迪注射液能改善患者生存质量,在增加体重方面两组差异有显著性;而艾迪注射液在辅助化疗减少相关毒副作用方面也具有一定效果。结论艾迪注射液联合化疗治疗结肠癌患者过程中,未发现明显毒副作用,能提高生存质量,减少化疗相关毒副作用。     

FOLFOX4方案治疗晚期大肠癌的临床观察

为了探讨FOLFOX4方案治疗晚期大肠癌的疗效和安全性,对37例初治或复治的晚期大肠癌患者,予FOL-FOX4方案化疗。全组37例均可评价疗效,初治组部分缓解(PR)7例,稳定(SD)13例,进展(PD)1例,客观有效率为33·3%,中位疾病进展时间8个月,中位生存期14个月;复治组PR3例,SD11例,PD2例,客观有效率为18·8%,中位疾病进展时间4个月,中位生存期7个月。毒副反应主要为中性粒细胞减少、消化道反应和神经毒性,均以Ⅰ~Ⅱ度为主,可耐受。初步临床观察结果表明,FOLFOX4方案治疗晚期大肠癌疗效肯定,安全性好,值得积极推广。     

FOLFOX4方案治疗晚期大肠癌的临床观察

为了探讨FOLFOX4方案治疗晚期大肠癌的疗效和安全性,对37例初治或复治的晚期大肠癌患者,予FOL-FOX4方案化疗.全组37例均可评价疗效,初治组部分缓解（PR）7例,稳定（SD）13例,进展（PD）1例,客观有效率为33.3%,中位疾病进展时间8个月,中位生存期14个月;复治组PR 3例,SD11例,PD 2例,客观有效率为18.8%,中位疾病进展时间4个月,中位生存期7个月.毒副反应主要为中性粒细胞减少、消化道反应和神经毒性,均以Ⅰ～Ⅱ度为主,可耐受.初步临床观察结果表明,FOLFOX4方案治疗晚期大肠癌疗效肯定,安全性好,值得积极推广.     

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。     

西妥昔单抗联合FOLFOX 4方案一线治疗转移性结直肠癌的临床观察

目的 观察西妥昔单抗联合FOLFOX 4方案一线治疗转移性结直肠癌的临床疗效和毒副反应。方法 回顾性分析2008年4月至2011年10月经组织病理学证实的转移性结直肠癌患者36例,其中治疗组（n=18）采用西妥昔单抗（500mg／m2 静滴120min,每周1次,使用6～12次）联合FOLFOX 4方案（奥沙利铂85mg／m2静滴2h,d1;左亚叶酸钙200mg／m2静滴2h,d1、d2;氟尿嘧啶400mg／m2静滴,d1、d2;氟尿嘧啶600mg／m2持续静脉泵入22h,d1、d2。14天为1周期,化疗不超过12个周期。）治疗。对照组（n=18）仅用FOLFOX 4方案化疗,同治疗组。结果 治疗组与对照组的客观缓解率分别为66.7％和22.2％（P＜0.05）,疾病控制率分别为94.4％和67.7％（P＞0.05）。治疗组和对照组痤疮样皮疹发生率分别为389％和0,其他不良反应包括骨髓抑制、恶心呕吐、神经毒性、肝脏损害及脱发等,差异均无统计学意义（P＞0.05）。结论 西妥昔单抗联合FOLFOX 4方案治疗转移性结直肠癌的近期疗效显著,毒副反应可耐受。     

Effects of reduced dose intensity of modified FOLFOX6 in patients with metastatic or recurrent colorectal cancer

The current study was conducted to retrospectively investigate the effects of reducing average relative dose intensity (ARDI) in response to adverse events on time to treatment failure (TTF) and overall survival (OS) in patients with metastatic or recurrent colorectal cancer receiving modified FOLFOX6 (mFOLFOX6) therapy between January 2006 and May 2010. Patients were divided into two groups based on ARDI: those with an ARDI of 85% or more (ARDI maintained; n = 12) and those with an ARDI of less than 85% (ARDI reduced; n = 37). In the ARDI-reduced group, out of a total of 402 treatment courses conducted, 25.9% involved treatment delays and 8.2% involved dose reductions, and the incidence rate of treatment delay was significantly higher than that of dose reduction (p < 0.001). Hematological toxicity was the main reason for both treatment delays and dose reductions. Reduced ARDI by dose reduction effectively prevented any increase in the severity of neutropenia and the treatment delays in the next courses, suggesting that the dose reductions were appropriately performed. Median TTF in the ARDI-maintained and ARDI-reduced groups was 5.2 and 5.8 months, respectively (p = 0.225). Median OS was 15.5 months and 33.9 months in the ARDI-maintained and ARDI-reduced groups, respectively (p = 0.347). These findings suggested that reductions in ARDI of mFOLFOX6 therapy for metastatic or recurrent colorectal cancer due to treatment delays and dose reductions in response to adverse events do not necessarily lead to shortened TTF and OS.     

西妥昔单抗联合化疗治疗转移性结直肠癌疗效与K-ras状态的关系

背景与目的：随着西妥昔单抗联合化疗在转移性结直肠癌患者中的不断应用,预测其治疗疗效的研究也越来越深入。本文旨在探讨转移性结直肠癌患者肿瘤组织中K—ras基因表达状态（野生型或突变型）及其与西妥昔单抗联合化疗疗效之间的关系。方法：2006年3月02008年6月期间应用西妥昔单抗联合化疗治疗转移性结直肠癌27例。采用聚合酶链反应（PCR）技术和直接测序法检测肿瘤组织中K-ras基因表达状态。分析K—ras基因表达状态与西妥昔单抗联合化疗疗效之间的关系。结果：全组27例患者中,K-ras野生型15例（55．6％）,K—FaS突变型12例（44．4％）。在K—FaS野生型中,西妥昔单抗联合化疗的总有效率（ORR）为66．7％,其中cR2例（13．3％）,PR 8例（53．3％）,中位无进展生存期（PFS）8个月。在K—ras突变型中,总有效率为25．0％,PR3例（25．0％）,中位PFS4个月。在K—ras野生型转移性结直肠癌患者中应用西妥昔单抗联合化疗的疗效明显优于K—ras突变型患者。结论：K-ras野生型是西妥昔单抗联合化疗疗效良好的预测指标。在西妥昔单抗联合化疗前明确患者的K—ras基因状态有助于选择合适的患者,获得最佳疗效。     

Pharmacoeconomic comparison between chronochemotherapy and FOLFOX regimen in the treatment of patients with metastatic colorectal cancer: a cost-minimization study

AIMS AND BACKGROUND: The addition of oxaliplatin to the widely employed De Gramont schedule (FOLFOX regimen) in patients with metastatic colorectal cancer improved their outcome with a moderate toxicity pattern. The adaptation of the delivery rate of 5-fluorouracil, leucovorin and oxaliplatin to circadian rhythms (chronotherapy) resulted in a very high drug tolerability with clinical results at least comparable to those achieved with the FOLFOX regimen. However, chronomodulated infusion seemed to be more expensive, requiring dedicated electronic pumps and several disposable materials. The present study aimed to compare the direct costs of the two regimens and to determine whether chronotherapy was effectively more expensive than the FOLFOX regimen. STUDY DESIGN: The direct costs of drug delivery devices derived from various publicly available sources and of toxicity management as extrapolated from two published studies considering comparable patient subsets were added and compared. RESULTS: Pump, central venous system and disposable materials for a single chronotherapy cycle were Euro 193 or Euro 212 according to whether the pumps were bought or rented, compared to Euro 58 for the FOLFOX regimen. Toxicity management costs were Euro 144 vs Euro 288 for the two schemes, respectively. Globally, a single course of chronotherapy cost Euro 337 or Euro 356, whereas a single FOLFOX cycle cost Euro 346. CONCLUSIONS: Direct costs for a single chronotherapy cycle appeared to be comparable to a single course of the FOLFOX regimen. In fact, the major material cost of chronochemotherapy devices was balanced by a better tolerability profile. The overall improvement in quality of life with chronochemotherapy affecting indirect costs, such as reduction of work, and intangible costs is worthy of further pharmacoeconomic attention.     

Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer

Background:

This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC).

Methods:

Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m⁻², folinic acid 400 mg m⁻², and 5-fluorouracil (400 mg m⁻² bolus then 2400 mg m⁻² over 46 h). Radiographic evaluation was performed every 8 weeks until progression. Primary endpoint was objective response rate.

Results:

Forty-four patients were enrolled and treated. Objective response rate was 63.6% (95% confidence interval 47.8–77.6); complete response was observed in four patients; median duration of response was 10.0 months (7.0–16.0). Median overall survival (OS) and progression-free survival (PFS) were 22.5 (11.0–30.0) and 10.0 months (7.0–12.0), respectively. Clinical outcome was better in patients with KRAS exon 2 wild type (median OS 30.0 months (23.0–NA); median PFS 12.0 (8.0–20.0)), compared with KRAS exon 2 mutant tumours (median OS 7.0 months (5.0–37.0); median PFS 7.0 (4.0–18.0)). The most common grade ⩾3 adverse events were neutropenia (29.5%), asthenia (27.3%), and rash (20.5%).

Conclusion:

First-line necitumumab+mFOLFOX6 was active with manageable toxicity in locally advanced or mCRC; additional evaluation of the impact of tumour RAS mutation status is warranted.     

西妥昔单抗与贝伐单抗分别联合FOLFOX4方案治疗晚期结直肠癌的对比研究

目的:比较西妥昔单抗与贝伐单抗分别联合FOLFOX4方案治疗晚期结直肠癌的临床疗效及安全性.方法:回顾性分析2008年9月至2012年9月经组织病理学证实的晚期结直肠癌患者49例,西妥昔单抗联合FOLFOX4方案组26例,贝伐单抗联合FOLFOX4方案组23例.两组患者在性别、年龄、病理类型、分期等方面大致平衡.观察各组临床疗效和治疗期间毒副反应.结果:贝伐单抗联合FOLFOX4方案治疗转移性结直肠癌有效率低于西妥昔单抗联合FOLFOX4方案(P<0.01).两组间毒副反应发生率差异无统计学意义(P>0.05).结论:西妥昔单抗联合化疗对K-Ras基因为野生型的转移性结直肠癌患者的疗效优于贝伐单抗,且耐受性好.     

A case of pseudomyxoma peritonei successfully treated with multidisciplinary treatment including modified FOLFOX6 regimen

We report a case of pseudomyxoma peritonei caused by carcinoma of the appendix, which was successfully treated with multidisciplinary treatment including modified FOLFOX6 regimen. A 45-year-old man was diagnosed as having peritoneal dissemination associated with cancer of the cecum or appendix. Seven cycles of mFOLFOX6 treatment resulted in a marked decrease in ascites and serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9. At laparotomy, a diagnosis of pseudomyxoma peritonei caused by cancer of the appendix was made. Intraperitoneal lavarge with 10,000 mL 5% glucose was performed after right hemicolectomy, omentectomy and removed of mucinous peritoneal nodules. Intraperitoneal chemotherapy comprised of 3000 mL low molecule dextran and 80 mg cisplatin was added on postoperative days 7 and 14. Modified FOLFOX6 regimen was started again two months postoperatively and reached 28 cycles. The patient does not show any sign of recurrence 12 months postoperatively.     

FOLFOX2 regimen in the treatment of advanced colorectal cancer: a comparison between elderly and young patients.

Colorectal cancers (CRC) are primarily disease of the sixth,seventh, and eighth decades of life. The probability of developingCRC increases from 0.06% in the first four decades of life to3–4% in the sixth and seventh decades in the Western world[1]. The prevalence of the disease and