CPT-11联合5-Fu/FA方案治疗34例晚期结直肠癌的疗效观察

目的评价CPT-11联合5-Fu／FA方案治疗晚期结直肠癌的临床疗效及毒副反应。方法全组34例,可评价疗效31例,其中3周方案14例,2周方案17例。3周方案：CPT-11 270mg／m^2静滴,d1,FA200mg／m。静滴,d1-5,5-Fu425mg／m^2静滴,d1-5,21d为1个周期,2个周期（6周）评价疗效;2周方案：CPT-11 180mg／m^2静滴,d1,FA200mg／m^2静滴,d1-2,5-Fu400mg／m^2静推,随后5-Fu600mg／m^2静滴22h,d1-2,14d为1个周期,3个周期（6周）评价疗效。结果CR1例,PR11例,SD14例,PD5例,总缓解率38．7％,总稳定率45．2％。中位缓解时间7．1个月,中位稳定时间8个月。主要毒副反应为迟发性腹泻（Ⅲ／Ⅳ度发生率为32．4％）及中性粒细胞减少（Ⅲ／Ⅳ度发生率为35．3％）。结论CPT-11联合5-Fu／FA两种方案治疗晚期结直肠癌有效率高,毒副反应可以耐受．可作为晚期结直肠癌的一线或二线化疗方案。     

伊立替康与氟尿嘧啶/亚叶酸钙方案治疗转移性结直肠癌的临床观察

为了评价和观察伊立替康(CPT-11)联合氟尿嘧啶(5-FU)与亚叶酸钙(LV)双周方案(FOLFIRI)治疗转移性结直肠癌的临床疗效和不良反应,对56例转移性结直肠癌患者采用FOLFIRI双周方案治疗,剂量为CPT-11180 mg/m2,静脉滴入90 min,d1,LV 200 mg/m2,静脉滴入,d1,d2,5-FU 400 mg/m2,静脉推注,d1,d2,5-FU600 mg/m2,持续静脉滴入22 h,d1,d2,14 d为1个周期.54例可评价疗效,CR 1例,PR 17例,SD 23例,PD 13例,有效率33.3%.不良反应主要为延迟性腹泻、中性粒细胞减少及胆碱能综合征.初步研究结果提示,FOLFIRI双周方案治疗转移性结直肠癌疗效肯定,安全性好,不良反应可耐受,值得临床推广应用.     

FOLFIRI方案治疗常规化疗失败晚期大肠癌的疗效分析

目的:探讨FOLFIRI方案治疗常规化疗失败晚期大肠癌患者的临床疗效和不良反应.方法:常规化疗失败的晚期大肠癌患者25例,开普拓(Irinotecan,CPT-11)180mg/m2,静脉滴注,d1;FA 200mg/m2,静脉滴注,d1-2;5-FU 400mg/m2静脉推注,然后5-FU 600mg/m2持续静脉滴注22h,d1-2,每2周重复,2次为1个周期,共行1-6个周期,中位周期1.5个.结果:25例患者,PR 9例,SD 10例,PD 6例,总缓解率36.0%,中位缓解时间3.0-13.5个月. 主要不良反应为迟发性腹泻和中性粒细胞减少,Ⅲ-Ⅳ度发生率分别为25.6%(11/43)和 41.9%(18/43).结论:FOLFIRI方案是治疗常规化疗失败晚期大肠癌的有效化疗方案,缓解率较高,迟发性腹泻和中性粒细胞减少为其主要不良反应.     

复发转移性结直肠癌FOLFOXIRI方案一线治疗的临床观察

目的:探讨FOLFOXIRI方案[伊立替康(CPT-11)+奥沙利铂(L-OHP)+5-氟尿嘧啶(5-FU)4-甲酰四氢叶酸(LV)]一线治疗复发或转移性结直肠癌的临床疗效和安全性.方法:对46例复发或转移性结直肠癌患者,采用FOLFO-XIRI方案治疗.CPT-11 150 mg/m2,持续静脉滴入90 min,d1;L-OHP 65 mg/m2,持续静脉滴入2 h,d2;LV 200 mg/m2,持续静脉滴入2 h,d2;5-FU 400 mg/m2,静脉推注,d2,d3;5-FU600 mg/m2持续静脉滴入22 h(泵),d2,d3;每14 d重复.观察近期疗效及不良反应.结果:46例患者中,完全缓解(CR)2例(4.3%),部分缓解(PR)25例(54.3%),稳定(SD)14例(30.4%),疾病进展(PD)6例(10.9%).未手术的患者中位疾病进展时间(TTP)10.2个月.安全性评价:发生卒最高的Ⅲ、Ⅳ度毒副反应是中性粒细胞减少13例(28.0%),腹泻6倒(13.0%).结论:FOLFOXIRI方案一线治疗复发或转移性结直肠癌安全、有效.     

伊立替康及CF联合5-FU或FUDR治疗消化道肿瘤毒副作用的比较

目的评价伊立替康及CF联合5-FU或FUDR的不同给药方案治疗晚期消化道恶性肿瘤的毒副作用。方法回顾性收集伊立替康及CF联合5-FU或FUDR的不同给药方案治疗晚期消化道肿瘤88例的临床资料,按化疗方案分为3组。A组33例,方案为:伊立替康150～180mg/m2静脉滴注d1,CF200mg/m2静脉滴注d1～2,5-FU400mg/m2静脉推注d1～2,5-FU600mg/m2持续静脉推注22hd1～2,每2周重复;B组27例,方案为:伊立替康240～270mg/m2静脉滴注d1,CF200mg/m2静脉滴注d1～5,5-FU750mg/m2静脉滴注d1～5,每3周重复;C组28例,方案为:伊立替康150～180mg/m2静脉滴注d1,CF200mg/m2静脉滴注d1～2,FUDR400mg/m2静脉推注d1～2,FUDR600mg/m2持续静脉推注22hd1～2,每2周重复。毒副作用指标为:白细胞减少、迟发性腹泻、口腔黏膜炎。结果 A组与C组白细胞减少的发生率高于B组(均P<0.05),而A组与C组之间无差别;迟发性腹泻及口腔黏膜炎的发生率3组间无明显差别。结论 5-FU静脉滴注组的白细胞减少的发生率低于...     

周剂量伊立替康二线治疗晚期转移性胃肠癌疗效观察

目的 周剂量伊立替康(CPT-11)联合5-氟脲嘧啶(5-Fu)及醛氢叶酸(LV)组成二线化疗方案,治疗一线化疗失败后的转移性胃肠癌患者,观察缓解率、安全性及生存期.方法 入组病例为转移性胃肠癌经一线化疗失败后的患者,CPT-11 60 mg/m2,LV100 mg/m2,5-Fu 500 mg/m2,每周1次,连续3周,每4周重复,每例至少接受2个疗程后评价疗效,患者最多接受6个疗程.结果 全组29例,25例肠癌中,CR 0例,PR 5例(20.0%),SD 9例(36.0%),PD 11例(44.0%),总有效率(CR+PR)为20.0%,疾病控制率为56.0%;4例胃癌中未见有效病例.所有患者的疾病进展时间为2～10个月,中位疾病进展时间4.0个月,生存期为5～28个月,中位生存期9.0个月.Ⅲ～Ⅳ度呕吐发生率34.5%,Ⅲ～Ⅳ度迟发性腹泻发生率为27.6%.结论 周剂量CPT-11联合5-Fu/LV为治疗晚期转移性结直肠癌有效的二线方案,毒副反应轻微,可供临床安全使用.     

伊立替康联合氟尿嘧啶/醛氢叶酸治疗转移性结直肠癌的临床观察

目的:评价伊立替康(CPT-11)联合氟尿嘧啶(5-FU)与醛氢叶酸(LV)治疗转移性结直肠癌的临床疗效及毒副反应。方法:48例转移性结直肠癌患者接受FOLFIRI方案化疗,化疗剂量CPT-11180mg/m2静脉滴入,d1,LV200mg/m2静脉滴入2h,5-FU400mg/m2静脉推注,d1,2400mg/m2持续灌注46h,每14d为1个周期,直至疾病进展或不良反应不能耐受。每3个周期评价疗效,观察毒副反应。结果:48例患者均可评价疗效及毒副反应。客观有效率为39.58%,疾病控制率为75%。48例患者中位疾病进展时间(TTP)6.8个月,中位生存时间17.5个月,中位TTP为8.1个月。不良反应主要是迟发性腹泻、中性粒细胞减少,乙酰胆碱综合征,恶心、呕吐,多为Ⅰ～Ⅱ度,Ⅲ～Ⅳ度发生率低,且均可控制。结论:FOLFIRI方案治疗转移性结直肠癌有较高的肿瘤控制率,安全性好,毒副反应可以耐受,并可减轻临床症状,延长患者的生存期。     

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。     

CPT-11联合CF/5-FU方案治疗胃肠道癌的Ⅰ期临床研究

目的探索CPT-11(开普拓)联合CF/5-FU治疗胃肠道癌的最大耐受剂量(MTD)和剂量限制性毒性(DLT).方法 CPT-11初始剂量为120mg/m2,然后150mg/m2,180mg/m2和200mg/m2 iv d1,递增剂量直至出现DLT.CF 200mg/m2iv 2h,然后5-FU 400mg/m2快速静滴,接着5-FU 600mg/m2持续静滴22h,第1天、第2天给药,2周重复.结果 20例胃肠道癌患者共完成化疗111周期,中位数6周期.MTD为200mg/m2,DLT为腹泻和WBC减少.结论我们推荐CPT-11180mg/m2联合CF/5-FR每2周重复的方法,作为国内PS为0～1胃肠癌患者的一线二线化疗方案.     

CPT-11联合草酸铂、5-FU方案二线治疗晚期卵巢癌的临床研究

目的:观察CPT-11联合草酸铂、5-FU作为二线治疗晚期卵巢癌的近期疗效及不良反应。方法:25例晚期卵巢癌一线治疗失败后,行二线化疗。具体方案为草酸铂85mg/m2,iv gtt,d1,8,15;5-FU 600mg/m2,iv gtt d1-5;CPT-11 60mg/m2,iv gtt,d2,9,16。28d为1周期,2个周期后评估疗效及不良反应。结果:可评价疗效25例,其中CR 7例,PR 5例,SD 6例,PD 7例,临床获益率72%。主要不良反应为恶心、呕吐、迟发性腹泻、肝脏损害、神经毒性和骨髓抑制等。结论:CPT-11联合草酸铂、5-FU方案二线治疗晚期卵巢癌有较好的疗效,且不良反应可以耐受。     

伊立替康联合氟尿嘧啶／四氢叶酸治疗晚期大肠癌的临床观察

目的观察和评价伊立替康(CPT-11)联合氟尿嘧啶(5-Fu)与四氢叶酸(LV)治疗晚期大肠癌的临床疗效和毒副反应。方法45例晚期大肠癌患者采用伊立替康(开普拓)180 mg/m2,化疗第1天静脉点滴90 min;LV 200 mg/d,ivgtt,d1~5;5-Fu 500 mg/d,ivgtt,d1~5,21 d为1周期,治疗2个周期以上评价疗效。结果全组45例均可评价疗效,CR 1例(2.2%),PR 16例(35.6%),NC16例(35.6%),PD 12例(26.7%),有效率37.8%。中位疾病进展时间(TTP)6.9个月。毒副反应主要为乙酰胆碱综合征、迟发性腹泻及中性粒细胞减少。结论伊立康替联合5-Fu/LV治疗晚期大肠癌疗效肯定,安全性好,毒副作用可耐受,值得进一步临床观察。     

Randomised phase II study of standard versus chronomodulated CPT-11 plus chronomodulated 5-fluorouracil and folinic acid in advanced colorectal cancer patients

In this study, a randomised phase II trial explored the effects of 6-h chronomodulated CPT-11 infusion in advanced colorectal cancer patients. Sixty-eight pre-treated patients were randomly assigned to CPT-11 administered at 180 mg/m2 on day 1, by 1-h infusion (Arm A) or 6-h sinusoidal infusion with peak timing at 5:00 a.m. (Arm B). All patients also received chronomodulated folinic acid/5-fluorouracil (FA/5-FU). Patients in Arm B obtained a 25.7% response rate for 7.0 months duration, a progression-free survival for 8.0 months and a median survival of 28 months. The same data in Arm A were 18.2%, 4.5, 6.0 and 18 months, respectively. No differences in drugs dose-intensity or increased toxicity with prolonged chronomodulated infusion were detected. Major grade 3-4 toxicity was diarrhoea: 10 patients in Arm A and 13 in Arm B. In conclusion, this study has shown that chronomodulated infusion of CPT-11 and FA/5-FU is safe, active and can be integrated with oxaliplatin (EORTC 05011) for the treatment of advanced colorectal cancer.     

CPT-11与5-Fu/LV方案治疗胃癌术后转移的临床价值

目的观察和评价伊立替康（CPT-11）联合氟尿嘧啶（5-Fu）与亚叶酸钙（LV）双周方案（FOLFIRI）治疗胃癌术后转移的临床疗效和不良反应情况。方法对62例胃癌术后转移患者采用FOLFIRI双周方案治疗,剂量为CPT-11180mg/m2,静脉滴入90min,d1;LV200mg/m2,静脉滴入,d1,d2;5-Fu400mg/m2,静脉推注,d1,d2;5-Fu600mg/m2,持续静脉滴入22h,d1,d2;14d为1个周期。结果 59例患者可评价疗效,其中CR2例,PR19例,SD26例,PD12例,有效率35.6%。不良反应主要为中性粒细胞减少、胆碱能综合征及延迟性腹泻。结论对于胃癌术后转移患者,FOLFIRI双周方案疗效肯定,不良反应可耐受,有重要的临床应用价值。     

Phase I study of CPT-11 and continuous 5-FU / l-leucovorin combination therapy(modified AIO regimen)in patients with metastatic colorectal cancer

A combination of CPT-11, continuous 5-fluorouracil(5-FU)and leucovorin(LV), the Arbeitsgemeinschaft für Internistische Onkologie(AIO)regimen, is widely used for the treatment of metastatic CRC. The efficacy and toxicity of this regimen, however, have not been determined in Japanese patients with metastatic CRC. Our objective was to evaluate the safety of the AIO regimen plus CPT-11 in Japanese colorectal carcinoma(CRC)patients. We investigated the maximum tolerated dose(MTD), dose-limiting toxicity(DLT), and recommended dose(RD)for CPT-11 and continuous 5-FU. CPT-11, 5-FU, and l-LV were administered on days 1, 8, and 15 of a 28-day cycle. The dose of CPT- 11 was escalated from 40 mg/m2 (level 1)to 80 mg/m2 (level 3). The 5-FU dose was then escalated from 1,000 mg/m2 (level 4)to 2,000 mg/m2 (level 5). If neither level met the criteria for the MTD, the recommended dose was defined as level 5, and the dose escalation was discontinued, because the maximum approved weekly dose of CPT-11 alone in Japan is 80 mg/m2 and the dose of 5-FU in the original AIO regimen was 2,000 mg/m2. A total of 18 patients were enrolled in this study. Hematological and non-hematological toxicity were infrequent and mild. There were no toxicities greater than grade 2 at each dose level. Level 5 did not meet the MTD criteria. Our results confirm that the modified AIO plus CPT-11 regimen is safe for Japanese patients. The recommended doses in the present study were CPT-11 80 mg/m2, 5-FU 2,000 mg/m2, and l-LV 250 mg/m2.     

Irinotecan and chronomodulated infusion of 5-fluorouracil and folinic acid in the treatment of patients with advanced colorectal carcinoma: a phase I study

BACKGROUND: Irinotecan (CPT-11) is an active drug in the treatment of patients with advanced colorectal carcinoma. The infusion of 5-fluorouracil (5-FU) according to circadian rhythms was used previously to decrease toxicity and to increase its therapeutic efficacy. The objective of this study was to establish the maximum tolerated dose (MTD) of CPT-11 together with a chronomodulated infusion of 5-FU and the l-form of folinic acid (FA). Secondary end points were the assessment of activity and quality of life (QoL). METHODS: Twenty-six patients with advanced colorectal carcinoma who had received previous treatment with 5-FU were entered on this Phase I study. At least three patients were recruited at each dose level. The CPT-11 starting dose was 175 mg/m(2) on Day 1 with an increase of 50 mg/m2 per dose level. A daily administration of chronomodulated 5-FU (900 mg/m2; peak delivery rate at 04:00) and FA (175 mg/m2; peak delivery rate at 04:00) for 5 days every 3 weeks was given with CPT-11. After the first three patients, the 5-FU dose was reduced to 700 mg/m2 per day due to toxicity. No intrapatient dose escalation was allowed. RESULTS: One hundred sixty-one courses were delivered. Dose-limiting toxicity was observed during the first course in seven patients (27%). Four patients developed neutropenia, with one patient reporting febrile neutropenia, two patients reporting severe stomatitis, and six patients reporting severe diarrhea. CPT-11 MTD was reached at 350 mg/m2 when a toxic death was observed with a recommended dose of 325 mg/m2. Six partial responses were observed (23%). The median duration of response and the progression free and overall survival rates were 199 days, 175 days, and 359 days, respectively. QoL was not affected by the treatment. CONCLUSIONS: The recommended dose for Phase II trials is 325 mg/m2 CPT-11 on Day 1, which is similar to the dose given as a single agent, together with a 5-day chronomodulated infusion of 700 mg/m2 5-FU and 175 mg/m2 FA. Intensification of this schedule every 2 weeks should be achievable.     

Irinotecan combined with bolus fluorouracil, continuous infusion fluorouracil, and high-dose leucovorin every two weeks (LV5FU2 regimen): a clinical dose-finding and pharmacokinetic study in patients with pretreated metastatic colorectal cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) and recommended dose of irinotecan (CPT-11) in combination with fluorouracil (5-FU) and leucovorin (LV), using a biweekly LV5FU2 regimen and increasing doses of CPT-11, and to assess the efficacy of this combination in pretreated patients with colorectal cancer (CRC). PATIENTS AND METHODS: All patients had metastatic CRC and a World Health Organization performance status of 0 or 1. CPT-11 was administered over a 90-minute infusion every 2 weeks at a range of dose levels (100, 120, 150, 180, 200, 220, and 260 mg/m(2)). LV5FU2 was started 1 hour after the end of the biweekly CPT-11 infusion and was also administered on day 2. RESULTS: Fifty-five patients were entered onto this trial; 549 cycles were administered. The MTD was not reached at 260 mg/m(2), and a dose level of 300 mg/m(2) was added. The MTD as defined in the protocol was not reached at this dose level either, but all patients had cycles delayed and/or required a dose reduction. This dose was deemed to be the MTD. To take into account both the toxicity of and compliance with the biweekly schedule, the recommended CPT-11 dose was established at 180 to 200 mg/m(2). Antitumor activity was observed at almost all dose levels, with an objective response rate of 22%. Median time to progression was 6.3 months and overall survival was 15 months. CONCLUSION: The biweekly CPT-11/LV5FU2 combination is feasible and safe, without overlapping toxicity. CPT-11 at 180 to 200 mg/m(2) in combination with LV5FU2 has been selected as the recommended dose for further studies.     

An alternating regimen of irinotecan/ 5-fluorouracil/folinic acid and oxaliplatin/ 5-fluorouracil/folinic acid in metastatic colorectal cancer: a Phase II trial

OBJECTIVE: To assess the feasibility and activity of a combination schedule with irinotecan (CPT-11), oxaliplatin (L-OHP), brief infusional fluorouracil (5-FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer (MCC) patients. METHODS: Fifty consecutive patients were treated with CPT-11 125 mg/m2 as a 90-min intravenous infusion, followed by FA 20 mg/m2 as an intravenous bolus, and 5-FU 500 mg/m2 over a 2-hour intravenous infusion on days 1 and 8. L-OHP was administered at 85 mg/m2 over 2 h on day 15, in combination with a FA 60 mg/m2 intravenous bolus and 5-FU 600 mg/m2 as a 2-hour intravenous infusion on days 15-16. The treatment was repeated every 4 weeks for a maximum of 9 cycles. RESULTS: Twenty-five of 50 assessable patients achieved a complete (n=5) or partial (n=20) response, leading to a response rate of 50% (95% CI 35-64%). Eighteen (36%) patients showed stable disease. The median time to tumor progression was 10.3 months (95% CI 9.6-10.9 months). After a median follow-up of 16.4 months, the median survival was not reached. Grade 3 neutropenia (8%), grade 3 nausea/vomiting (6%) and grade 3 diarrhea (2%) were the major adverse events. CONCLUSION: This alternating three-drug regimen is very well tolerated, manageable and effective in terms of activity and time to progression.     

FOLFIRI regimen for metastatic or recurrent colorectal cancer

Irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and Leucovorin (LV) became the standard first-line chemotherapy for colorectal cancer in the U.S. and Europe in 2000, largely owing to the results of controlled randomized phase III trials of 5-FU/LV with or without CPT-11. One of the regimens for CPT-11 plus infusional 5-FU/LV therapy is the FOLFIRI regimen. This regimen consists of CPT-11 180 mg/m(2) as a 90-min infusion on day 1 and l-LV 200 mg/m(2) as a 2-h infusion during CPT-11, immediately followed by a bolus dose of 5-FU 400 mg/m(2) and a 46-h continuous infusion of 2,400 mg/m(2) every 2 weeks. FOLFIRI, as well as oxaliplatin/5-FU/LV therapy (FOLFOX), is an internationally accepted standard chemotherapy for metastatic colorectal cancer. Safe use of this effective regimen requires adequate supportive therapy in Japan, as well as in Western countries.