FOLFOX方案一线治疗转移性或复发性晚期大肠癌的疗效分析

目的：评价草酸铂、氟尿嘧啶联合醛氢叶酸（FOLFOX方案）一线治疗转移性或复发性晚期大肠癌的临床疗效及不良反应。方法：对于未接受过姑息性化疗的转移性或复发性大肠癌患者给予草酸铂100mg／m^2于第l天静脉滴注2h、醛氢叶酸400mg／m^静脉滴注2h，氟尿嘧啶400mg／m^静脉推注．随后氟尿嘧啶2600～3000mg／m^持续静脉灌注46h。结果：105例患者中97例患者可以评价疗效，总有效率为35．1％，CR率为9．3％，PR率为25．8％；33．0％的患者为SD，另有31．9％的患者PD。中位疾病进展时间（TTP）为7．7个月，中位总生存时间（OS）为20．5个月。1年及2年的总生存率分别为68．0％和32．0％。按照NCI—CTC不良反应分级，Ⅲ．Ⅳ级不良反应发生率分别为：白细胞降低12．3％，贫血11.3％；呕吐4．1％，腹泻7．2％。Ⅲ度外周神经毒性发生率为5．1％。曾接受过根治性手术治疗的患者的生存优于未接受过手术或仅接受过姑息性手术治疗的患者的生存（P=0．0658）；化疗前患者的CEA、ALP及LDH水平对患者的预后无明显影响（P〉0．05）。结论：FOLFOX方案一线治疗转移性或复发性晚期大肠癌是一个有效的方案．并且不良反应可耐受。     

FOLFOX4方案治疗老年晚期大肠癌的疗效观察

奥沙利铂（L—OHP）是新一代铂类抗癌药,以L—OHP为主的联合化疗方案已被美国FDA和欧洲EU批准作为晚期大肠癌的一线和二线治疗。我们于2002年3月-2004年4月采用国产奥沙利铂（江苏恒瑞制药有限公司产品,商品名艾恒）为主联合氟尿嘧啶（5-FU）及亚叶酸钙（CF）组成的FOLFOX4方案治疗老年晚期大肠癌26例,取得了较好的疗效,现总结报告如下：     

FOLFOX4方案治疗晚期大肠癌近期疗效观察

目的：研究草酸铂（L-OHP）与氟尿嘧啶（5-Fu）及亚叶酸钙（CF）联合应用治疗晚期大肠癌的疗效和毒副反应。方法：采用L-OHP85mg/m2,静脉滴入2h,d1;CF200mg/m2,静脉滴入2h,d1、d2;5-Fu400mg/m2,静脉注入（CF滴完后）,d1、d2;5-Fu600mg/m2持续静滴22h,d1、d2;每2周重复,28天为一周期。结果：总有效率为40.5%,中位疾病无进展时间8个月、毒副反应以骨髓抑制、感觉神经毒性为主,无Ⅳ度毒副反应。结论：L-OHP、5-Fu、CF联合应用治疗晚期大肠癌疗效肯定,毒副反应能耐受。     

FFL方案治疗转移性大肠癌的近期疗效观察

目的探讨FFL(草酸铂+5-氟脲嘧啶+亚叶酸钙)方案对转移性大肠癌的近期疗效.方法对22例大肠癌术后出现局部复发或转移的病人采用FFL方案化疗,其中初治6例,复发后治疗16例.结果疗效为完全缓解者(CR)2例,部分缓解者(PR)8例;总有效率为45.5%.结论对于转移性大肠癌FFL方案可获得较高的缓解率,同时化疗反应轻微.     

HCPT联合FOLFOX4方案治疗晚期胃癌、大肠癌疗效观察

目的评价羟基喜树碱(HCPT)联合FOLFOX4方案治疗晚期胃癌、大肠癌的近期疗效和毒副反应。方法28例晚期消化道癌患者,先给予草酸铂(L-OHP)85mg/m2静脉点滴2h d1,亚叶酸钙(CF)200mg/m2静脉点滴2h d1~d2,随后5-氟尿嘧啶(5-FU)400mg/m2静脉推注,5-FU600mg/m2静脉点滴22h d1~d2,同时给予HCPT6 mg/m2静脉点滴3h d1~d3。2周重复,4周期后评价疗效。结果全组28例,其中完全缓解(CR)2例(7.1%),部分缓解(PR)16例(57.1%),稳定(SD)4例(14.3%),进展(PD)6例(21.4%)。总有效率(CR PR)64.3%。胃癌16例,11例有效,有效率68.8%。大肠癌12例,7例有效,有效率58.3%。毒副反应主要是恶心呕吐,白细胞减少,神经感觉毒性,无化疗相关死亡。结论HCPT联合FOLFOX4方案治疗晚期消化道癌疗效肯定,毒副反应能耐受。     

草酸铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌36例临床观察

目的 观察草酸铂(L-OHP)联合氟尿嘧啶(5-Fu)和亚叶酸钙(CF)治疗晚期大肠癌的近期疗效和毒副反应.方法 经病理组织学诊断的晚期大肠癌36例,用L-OHP 130 mg/m2,静脉滴注4h,每天1次;CF 200 mg,静脉滴注2 d,继以5-Fu 400 mg/m2,dl,d2,静脉滴入,5-Fu600 mg/m2,微量泵入A48 h以上,每3周重复1次,作为1个治疗周期,治疗2个周期后评定疗效.结果 36例总有效率为13例(37.1﹪),完全缓解1例(2.8﹪),部分缓解12例(33.3﹪),无变化14例(38.9﹪),进展9例(25﹪).主要的毒副作用为神经毒性、骨髓抑制、恶心呕吐等,无治疗相关性死亡患者.结论 L-OHP联合大剂量CF及5-Fu治疗晚期大肠癌疗效较好,毒副反应能为患者耐受,值得临床推广应用.     

得力生联合OLF方案治疗晚期大肠癌的临床研究

目的：比较得力生-OLF方案与OLF方案对晚期大肠癌患者的疗效、不良反应。方法：A组（34例）接受得力生-OLF方案治疗;B组（33例）接受OLF方案治疗。两组均以3周为1个周期,重复3个周期。结果：A、B两组（CR＋PR）分别为44.2%及36.3%（P〉0.05）;中位生存期A组46周,B组41周（P〈0.05）;白细胞减少及恶心呕吐反应B组均较A组明显（P〈0.05）;两组均未发现其他严重的不良反应。临床受益疗效A组高于B组（P〈0.05）。结论：得力生配合OLF方案与单纯OLF方案治疗晚期晚期大肠癌的客观疗效无明显差异,但前者不良反应小,中位生存期长。     

氟脲嘧啶持续灌注为主方案治疗晚期大肠癌

目的研究草酸铂、羟基喜树碱分别与5-氟脲嘧啶/亚叶酸钙持续静脉输注方案治疗的疗效、毒性对照以找到一种临床上更有效方案.方法64例病人随机分为两组:A组3l例;草酸铂120mg/m2静滴d1,5-氟脲嘧啶0.5/m2连续5天持续静脉输注,亚叶酸钙200mg/m2静滴2小时d1-5.B组33例;羟基喜树碱8mg/m2静滴d1-5,5-氟脲嘧啶与亚叶酸钙同A组.结果A组有效率51.6%,B组为27.3%,有显著差异(P＜0.05).主要的毒副反应为血液毒性,两组间毒副反应无统计学差异.结论草酸铂联合5-氟脲嘧啶/亚叶酸钙持续静脉输注方案治疗晚期大肠癌疗效高,优于羟基喜树碱联合方案,值得临床一线应用.     

奥沙利铂联合LF方案治疗晚期大肠癌

本科于2001年1月至2002年8月用奥沙利铂(L-OHP)联合氟尿嚓Ark (5-Fu)、亚叶酸钙(C F)治疗晚期大肠癌取得较满意疗效, 现报告如下。     

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。     

L-OHP联合不同使用方法5-FU/FA方案治疗晚期结直肠癌的疗效比较

目的比较L-OHP(奥沙利铂)联合不同使用方法5-FUFA(氟尿嘧啶亚叶酸钙)方案治疗晚期结直肠癌的疗效及不良反应。方法62例患者均可参加疗效评价。ArmA方案(32例):L-OHP130mgm2静滴d1;FA200mg(m2·d),5-FU425mg(m2·d)分别静滴,均d1～5,每3周重复,3周为1周期。ArmB方案(30例):L-OHP85mgm2静滴d1;FA200mg(m2·d)静滴后,5-FU400mg(m2·d)静推,然后5-FU600mg(m2·d)持续微量泵注射22小时,d1～2,每2周重复,4周为1周期。结果ArmA方案CR1例,PR14例,总有效率46.9%。ArmB方案CR1例,PR11例,总有效率40%。严重不良反应较少。结论L-OHP联合不同使用方法5-FUFA方案治疗晚期结直肠癌均有较高疗效,毒副作用相近。     

Molecular markers of chemotherapeutic response and toxicity in colorectal cancer

Outcomes in colorectal cancer have improved over the last 15 years; this is in part due to the optimization of 5-fluorouracil schedules and the introduction of new and effective chemotherapeutic agents, such as irinotecan and oxaliplatin. However, not all patients respond to these agents and a proportion may suffer severe side effects from particular chemotherapy drugs. These observations have resulted in a concerted research effort to identify markers of chemotherapy efficacy and toxicity. Here we review the evidence for using molecular markers to individualize chemotherapy treatment in colorectal cancer.     

晚期结直肠癌的化疗进展

转移性结直肠癌是癌症相关死亡的主要原因之一。对于所有转移性疾病来说手术切除可以治愈部分患者，但大部分患者需要考虑全身化疗作为最佳的姑息治疗。多年来，晚期结直肠癌的有效治疗局限于氟尿嘧啶。20世纪90年代出现的另外两个药物伊立替康和奥沙利铂被发现对晚期结直肠癌有效。近来，新的分子靶向药物bevacizumab和cetuximab首次显示了疗效。这里我们回顾了晚期结直肠癌治疗的最新进展和对于这些患者的最佳治疗。     

Modified de Gramont with oxaliplatin in the first-line treatment of advanced colorectal cancer

We previously reported high activity for oxaliplatin and a modified de Gramont regimen (OxMdG) in a single centre study of patients with metastatic colorectal cancer. We now report results with a further 56 patients treated at 14 centres. Low rates of grade 3 and 4 toxicity were seen, with no toxic deaths. Objective response rates were CR/PR=53%; NC=34.7%; PD=12.2%. Median time to progression was 8.3 months and overall survival was 14.5 months. This regimen is more convenient than those based around the conventional de Gramont regimen but is highly active and well tolerated; it forms part of a current UK MRC phase 3 trial.     

FOLFOX6方案与DOF方案治疗晚期胃癌的临床疗效和安全性比较

目的比较奥沙利铂+亚叶酸钙+氟尿嘧啶(FOLFOX6)方案和多西他赛+奥沙利铂+氟尿嘧啶(DOF)方案治疗晚期胃癌的临床疗效和安全性。方法回顾性分析93例Ⅲ～Ⅳ期胃癌患者的病历资料,依据治疗方案的不同将患者分为FOLFOX6组(n=48)和DOF组(n=45)。比较两组患者化疗2个周期后的临床疗效,评定不良反应发生情况。结果化疗2个周期后,DOF组患者的总有效率和疾病控制率分别为33.3%(15/45)和84.4%(38/45),分别高于FOLFOX6组的18.8%(9/48)和68.8%(33/48),差异均有统计学意义(P﹤0.05)。治疗过程中,DOF组患者的消化道不良反应较FOLFOX6组严重,差异有统计学意义(Z=-2.516,P﹤0.05);两组患者骨髓抑制和外周神经炎的发生情况比较,差异均无统计学意义(P﹥0.05)。结论与应用FOLFOX6方案治疗晚期胃癌相比,应用DOF方案的疗效更好,虽然消化道不良反应发生率较高,但患者均可耐受。     

Oxaliplatin, Fluorouracil and Leucovorin （FOLFOX） as First-line Chemotherapy for Metastatic or Recurrent Colorectal Cancer Patients

OBJECTIVE To investigate the efficiency and safety of the oxaliplatin, fluorouracil(5-FU)and leucovorin regimen(FOLFOX)in previously untreated patients with metastatic or recurrent colorectal cancer. METHODS Previously untreated patients with metastatic or recurrent colorectal cancer received 100 mg/m2 of oxaliplatin intravenously(IV)over 2 h on day 1,and IV 400 mg/m2 of leucovorin over 2 h followed by a bolus of 400 mg/m2 of 5-FU.Then 2,600~3,000 mg/m2 of 5-FU was administered by continuous infusion over 46 h. RESULTS An evaluated response rate was determined for 97 of 105 treated patients.The overal response rate was 35.1%,9 patients(9.3%) had a complete response and 25 patients(25.8%)a partial response.Thirty-two patients(33.0%)developed stable disease and 32.0%of the patients progressed.The median time to progression(TTP)was 7.7 months and the median overal survival 20.5 months.One and 2-year survival rates were 68%and 32%.Toxic effects based on the National Cancer Institute-Common Toxicity Criteria(NCI-CTC),reaching grade 3/4 were:neutropenia 12.3%, anemia 11.3%,vomiting 4.1%and diarrhea 7.2%.Grade 3 neuropathy was 5.1%.The overall survival rate of patients who had received a radical resection was superior to the patients who had not received a operation,or had received a pal iative resection(P=0.0658).The serum levels of CEA,ALP and LDH had no relationship with survival(P>0.05). CONCLUSION The FOLFOX regimen containing oxaliplatin,5-FU plus leucovorin was an efficacious regimen with good tolerability in previously untreated metastatic or recurrent colorectal cancer patients.     

FOLFOX4治疗52例晚期大肠癌

[目的]观察FOLFOX4方案治疗晚期大肠癌的疗效及毒副反应。[方法]对52例初治或复治的晚期大肠癌患者,予FOLFOX4方案化疗(奥沙利铂 亚叶酸钙 5-氟尿嘧啶)。[结果]全组52例均可评价疗效及毒副反应。总有效率为30.7%。初治患者CR1例,PR8例,SD10例,PD2例,有效率为45%;中位疾病进展时间10个月,中位生存期17个月。复治患者PR7例,SD20例,PD5例,有效率为21.9%;中位疾病进展时间6个月,平均生存期12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,以Ⅰ～Ⅱ度为主。[结论]FOLFOX4方案治疗晚期大肠癌疗效肯定,安全性好。     

A 'modified de Gramont' regimen of fluorouracil,alone and with oxaliplatin,for advanced colorectal cancer

The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified 'Modified de Gramont' (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m(-2)), then ambulatory 46-h fluorouracil infusion (2000-3600 mg m(-2), cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m(-2). Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m(-2) bolus + 2800 mg m(-2) 46-h infusion. A lower dose of 400 mg m(-2) bolus + 2400 mg m(-2) infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC(0-48 h)) at this lower dose is equivalent to dG. With OxMdG, grade 3-4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial.     

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.     

Phase II study of UFT and oxaliplatin in first-line treatment of advanced colorectal cancer

The purpose of this study was to evaluate the efficacy, assessed as response rate, and toxicity of UFT (Tegafur-Uracil) in combination with oxaliplatin as first-line treatment of advanced colorectal cancer (CRC). In all, 84 patients with recurrent or metastatic CRC with measurable disease were included. Treatment consisted of oxaliplatin 85 mg m(-2) in 120-min intravenous (i.v.) infusion on days 1 and 15; i.v. l,leucovorin (l,LV) 250 mg m(-2) given in 2 h on day 1, followed by oral UFT 390 mg m(-2) on days 1-14, and oral l,LV 7.5 mg/12 h on days 2-14. Cycles were repeated every 28 days. A total of 492 cycles of chemotherapy were delivered with a median of six per patient (range 1-12). There was one complete response (1%) and 28 partial responses (34%) for an overall response rate of 35% (95% confidence interval (CI): 24-46%). A total of 36 patients (44%) had stable disease, whereas 17 (21%) had a progression. The median time to progression was 7.3 months and the median overall survival was 16.8 months. A prescheduled preliminary analysis was performed after inclusion of 16 patients who detected a high gastrointestinal toxicity, which led to a reduction of the UFT dose to 300 mg m(-2). With this new dosage, grade 3-4 diarrhoea and grade 3-4 nausea/vomiting dropped to 21 and 14% of patients, respectively. Other grade 3-4 toxicities were stomatitis in one (1%), anaemia in three (5%), neutropenia in two (3%), thrombocytopenia in one(1%), fatigue in six (9%), peripheral sensory neuropathy in nine (14%) and laryngopharyngeal dysesthesia in two patients (2%). The combination of oxaliplatin and UFT-l,LV is an active, easy-to-administer regimen with moderate toxicity. Hence, this regimen is worthy of further investigation.