结直肠癌5—FU和亚叶酸辅助化疗的评价

目的：评估５－ＦＵ和亚叶酸辅助化疗能否提高结直肠癌根治术的疗效。方法：自１９８８年以来共有２２５例结直肠癌根治术应用５－ＦＵ和亚叶酸辅助化疗，术后每月一次，连续５天给予亚叶酸１５０ｍｇ和５－ＦＵ１．０ｇ／日，６～９个疗程，其中随访率５年可作评估６６例，包括结肠癌３８例和直肠癌２８例，结果：６６例的５年生存率为６６．６７％，结肠癌为７３．６８％，直肠癌为５７．１４％。Ｄｕｋｅｓ－中国改良分期Ａ期的５     

结直肠癌5-FU敏感性相关基因的文献计量学与生物信息学分析

目的对结直肠癌5-FU敏感相关基因的临床资料进行分析,为寻找5-FU敏感相关关键基因提供参考。方法以Embase、Pubmed为文献检索数据库,对纳入的105篇文献分别对其出版年、国家、期刊、研究机构、作者及所研究基因进行计量学与生物信息学分析。结果结直肠癌5-FU敏感相关基因文章在发表年限上呈波动式分布;发文量最多的国家、期刊、机构、作者分别为USA、Clin Cancer Res、University of Southern California;W.Ichikawa;其中TYMS是最为热点的基因(36篇);105篇文献共涉及57个结直肠癌5-FU敏感相关基因,其蛋白主要涉及细胞增殖、细胞周期调控、细胞周期等。Hub基因共有21个,bottleneck基因有16个。结论结直肠癌5-FU敏感相关基因已形成多基因预测模型趋势,TP53、YMS等基因在结直肠癌5-FU疗效预测中可能起关键作用。     

氟铁龙与亚叶酸联合治疗进展期结直肠癌的初步体会

结直肠癌的发生率目前正呈迅速上升趋势，已成为严重威胁人们健康和生命的常见病。虽然外科手术仍是治疗结直肠癌的主要手段，但人们已越来越认识到在进一步提高疗效中综合治疗的重要性。化疗是综合治疗中的重要组成部分，５－ＦＵ则是当前应用最广泛的首选药物，５－ＦＵ...     

国产奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期结直肠癌的临床观察

目的评价奥沙利铂(L-OHP)联合氟尿嘧啶(5-Fu)、亚叶酸钙(CF)方案治疗晚期结直肠癌的疗效与毒副反应.方法奥沙利铂130 mg/m2,静滴4 h,第1天;亚叶酸钙200 mg静脉滴注2 h,5-Fu 300 mg/m2,持续静滴6～8 h,第1～5天(亚叶酸钙滴完后用);21 d为1周期,行2周期治疗后评价疗效.结果全组完全缓解(CR)1例,部分缓解(PR)12例,总有效率(CR PR)为43.3%.毒性反应以骨髓抑制、感觉性神经毒性为主,多为Ⅰ～Ⅱ度,其中白细胞减少发生率为46.7%,感觉性神经毒性发生率为77.7%,无化疗相关死亡.结论奥沙利铂联合氟尿嘧啶、亚叶酸钙治疗晚期结直肠癌疗效肯定,毒副反应能耐受.     

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。     

叶酸与结直肠肿瘤

流行病学和试验研究提示叶酸缺乏及叶酸代谢异常和结直肠肿瘤发病风险升高有关。亚甲基四氢叶酸还原酶（MTHFR）是调节叶酸代谢的关键酶，MTHFRC677T基因多态及饮酒影响叶酸代谢，从而影响结直肠肿瘤的发病风险。     

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.     

亚叶酸/氟尿嘧啶持续静脉灌注治疗晚期结直肠癌

结直肠癌是十大常见肿瘤之一 ,在我国发病率呈逐年上升趋势。因早期诊断困难 ,多数患者治疗效果差。近年来以手术为主的综合治疗使结直肠癌的生存率有了一定提高 ,但仍有 1/ 3的患者会出现复发 ,近半数患者死于转移[1] 。氟尿嘧啶是治疗晚期结直肠癌的主要药物 ,单药有效率≤15 % [2 ] 。我们采用亚叶酸 (ｌｅｕｃｏｖｏｒｉｎ ,ＬＶ)、氟尿嘧啶 (ｆｌｕｏ ｒｏｕｒａｃｉｌ,5 ＦＵ)持续静脉灌注治疗晚期结直肠癌 34例 ,观察其近期疗效和毒副作用。材料和方法一　研究对象　 1998年 4月～ 2 0 0 1年 4月我院收治晚期结直肠癌 34例。男 19例…     

持续静脉滴入低剂量5-FU联合亚叶酸钙和奥沙利铂治疗晚期结直肠癌疗效观察

以生化调节剂亚叶酸钙(CF)增效5氟尿嘧啶(5FU)治疗晚期大肠癌的方案已广泛用于临床。奥沙利铂是第3代铂类抗癌药,对结直肠癌具有较好的疗效。我科应用低剂量5FU持续静脉滴注联合CF和奥沙利铂治疗晚期结直肠癌22例,结果总结报道如下。1临床资料1.1一般资料2002年5月～2004年12月     

奥沙利铂联合5-氟尿嘧啶/亚叶酸钙3周重复方案用于结直肠癌术后辅助化疗的临床观察

目的:探讨奥沙利铂(oxaliplatin,OXA)联合5-氟尿嘧啶(5-fluorouracil,5-FU)和亚叶酸钙(leucovorin,CF)3周重复方案用于结直肠癌术后辅助化疗的临床价值.方法:98例Ⅱ～Ⅲ期结直肠癌患者根治术后接受OXA联合5-FU/CF 3周重复方案辅助化疗,共化疗6个周期.患者化疗结束后每3个月进行1次全面复查,观察无病生存期及1和2年的无病生存率.结果:本组患者总的2年无病生存率为74.5%,其中Ⅱ和Ⅲ期患者的2年无病生存率分别为87.0%和63.5%.化疗期间的主要不良反应为Ⅰ～Ⅱ度外周神经毒性、中性粒细胞减少及腹泻,Ⅲ～Ⅳ度不良反应少见.结论:OXA联合5-FU/CF 3周重复方案用于结直肠癌术后辅助化疗疗效明确,患者耐受性好,是结直肠癌术后辅助化疗的理想选择.     

High and Low Dose Folinic Acid, 5-Fluorouracil Bolus and Continuous Infusion for Poor-Prognosis Patients with Advanced Colorectal Carcinoma

Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FUbased chemotherapy. Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yetserve as the internationally accepted Gold Standard . A bimonthly regimen of high dose leucovorin is reportedto be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses andsurvival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. Patients andMethods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramontand Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid (200 mg/m2), glucose 5%,5-FU (400 mg/m2) and 22 hr. CIV (600 mg/m2) for two consecutive days every two weeks. These patients hadfailed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteenpatients (six below 60 years) with progressive disease were subjected to low dose folinic acid (20 mg/m2)for fivedays, 5FU(425 mg/m2) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty daysand responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positiveprognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria.Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11(32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade≥2 events was assessed. The response duration was extended (12 months) in a few patients with age above sixtyyears treated by high dose bimonthly regimen of 5FU/LV. Conclusion: The regimens are safe and effective inadvanced colorectal carcinoma patients with poor general status.     

奥沙利铂联用氟脲嘧啶、亚叶酸钙治疗晚期大肠癌的临床研究

目的　观察奥沙利铂联用氟脲嘧啶、亚叶酸钙治疗晚期大肠癌 (ACRC)的疗效和安全性。方法　收治晚期大肠癌患者 3 0例 ,采用L_OHP 13 0mg/m2 静脉滴注 4hd1 ;CF 2 0 0mg/m2 静脉滴注半小时后 5_Fu 5 0 0mg/m2 静脉滴注 6hd1～ 5,每 3周重复。结果　部分缓解 (PR) 9例 ,稳定 (SD) 8例 ,进展 (PD) 8例 ,总有效率 3 6%。毒性反应主要为感觉神经毒性 ( 90 %) ,其次为恶心呕吐 ( 60 %)和腹泻 ( 4 6 7%)。骨髓抑制毒性小。结论　L_OHP联合 5_Fu、CF治疗大肠癌疗效肯定 ,耐受性良好 ,值得临床进一步研究     

Phase II Trial of 5-Fluorouracil and High-Dose Folinic Acid in Advanced Renal Cell Cancer

Summary

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated with high-dose folinic acid (HDFA): 200 mg/m² i.v. and 5-fluorouracil (5-FU): 370 mg/m² i.v. for 5 consecutive days every 28 days. Severe oral mucositis (WHO grade III-IV) was experienced by two patients, whereas hematological toxicity was mild. No complete or partial remission was observed. Short-lasting stable disease occurred in 8 patients (median = 5 months, range 2-11). This combination does not need further evualuation in patients with RCC.     

Retrospective Comparison of Two Different Schedules of Irinotecan, 5-Fluorouracil and Folinic Acid in Previously Untreated Patients with Advanced Colorectal Carcinoma: A Single Institution Experience

Abstract

Purpose: To compare efficacy and tolerability of weekly irinotecan combined with 5-fluorouracil (5-FU) bolus and folinic acid (FA) regimen (IFL) versus biweekly irinotecan with infusional 5-FU and FA (FOLFIRI) in patients (pts) with advanced stage colorectal cancer.

Patients and Methods: Treatments outcome of 86 pts (IFL - 38 pts, FOLFIRI - 48 pts) was evaluated. Chemotherapy regimens were as follows: IFL - intravenous (i.v.) infusion irinotecan 125 mg/m² over 90 min and 5-FU 500 mg/m² preceded by FA 20 mg/m² both given by i.v. bolus injection, all repeated on days 1, 8, 15 and 22 every 6 weeks; FOLFIRI - i.v. irinotecan 180 mg/m² on days 1 and 15 with subsequent FA 200 mg/m² administered as a 2-hour infusion and i.v. bolus injection of 400 mg/m² 5-FU immediately followed by 22-hour i.v. infusion of 600 mg/m² 5-FU on days 1, 2, 15 and 16 every 4 weeks. Treatment continued until disease progression or unacceptable toxicity.

Results: A total of 152 (mean - 4) IFL cycles and 328 (mean - 6) FOLFIRI cycles were administered. Average dose intensity was 0.8 and 0.78 respectively. Toxicities were mild and manageable for both regimens evaluated. Overall response rate was 36.8% in IFL arm and 44.7 % in FOLFIRI arm. At the median follow-up of 16 months in IFL arm and 14 months in FOPFIRI arm the two year survival was 38% and 45%, the median survival was 18 months and 21.5 months, and the median progression free survival was 6 months and 9.4 months respectively.

Conclusions: In our experience, both IFL and FOLFIRI regimens have acceptable toxicity at a similar level of dose intensity. Compared to IFL, FOLFIRI seems to improve progression-free survival.     

Clinical Trial of Continuous Infusion of 5-Fluorouracil Using an Ambulatory Pump for Metastatic Colorectal Cancer

A clinical trial was conducted in order to evaluate the anti-tumoreffect and toxicity of a continuous ifusion of 5-fluorouracil(5-FU) for metastati colorectal cancer. Two-hundred and fiftymg/m²/day 5-FU was administered as a continuous infusion throughan indwelling central venous catheter with ambulatory pump.Twenty patients with metastatic colorectal cancer which couldbe measured or evaluated were enrolled in the trial. The objectiveresponse rate was 35% (95% confidence interval, 14–56%).The response rates by site were 33% in liver, 17% in lung, 60%in lymph nodes, 50% in adrenal gland and 50% in primary lesion.The major toxicity was stomatitis (50%; grades 2 and 3 on EasternCooperative Oncology Group (ECOG) criteria) and hand-foot syndrome(40%; grades 2 and 3 on ECOG criteria). The sequence of toxicitywas stomatitis first, followed by hand-foot syndrome. The mediancumulative dose of 5-FU from the initiation of therapy to theonset of toxicity was 7125 mg in stomatitis and 17,875 mg inhand-foot syndrome. These toxicities were mild and reversibleafter a short interruption to the 5-FU infusion. Neither hematologicaltoxicity nor serious catheter-related complications were observed.We concluded that continuous infusion of 5-FU was a feasibletreatment for the patient with metastatic colorectal cancer,and manageable on an out-patient basis     

Bimonthly Chemotherapy with Oxaliplatin,Irinotecan, Infusional 5-Fluorouracil/Folinic Acid in Patients with Metastatic Colorectal Cancer Pretreated with Irinotecan- or Oxaliplatin-Based Chemotherapy

Abstract

This study was conducted to assess the tolerability and efficacy of a ternary bi-monthly irinotecan (CPT-11) - oxaliplatin (OHP) - infusional 5-fluorouracil (5-FU)/folinic acid (FA) combination in advanced colorectal cancer patients who had received prior CPT-11 and/or OHP-based chemotherapy regimen. Colorectal cancer patients were given bimonthly CPT-11 as a 90-min infusion, followed by OHP (85 mg/m²), FA (200 mg/m²) 2-h infusions and 5-FU (48-h infusion). CPT-11 and 5-FU doses were escalated as reported below. 26 patients were recruited. Fourteen patients had received a prior CPT-11-, 6 patients a prior OHP-based chemotherapy regimen and 6 patients both regimens. Three dose levels were investigated: CPT-11 100, 120 and 140 mg/m² and 5-FU 1500, 1800 and 2100 mg/m² in 6, 12 and 8 patients, respectively. All patients were evaluable for toxicity, 24 for antitumor activity. At all dose levels toxicity was ac-ceptable. Grade 4 toxicity occurred in two patients only (neutropenia in one case and stomatitis in another one, 3.8%). Grade 3 toxicities included nausea and vomiting (34.6%), asthenia (26.9%), neurosensory toxicity (15.4%), neutropenia (3.8%) and di-arrhea (3.8%). Hematological toxicity was infrequent and generally mild. At the third dose level, a higher, although not significantly different incidence of hematological and neurosensory toxicity (both occurring in 62.5% of cases, all grades) was observed compared to the other two, while nausea and vomiting were significantly less frequent (37.5% vs 100%). Overall, we observed 2 complete responses, 9 partial responses (OR 45.8%), 8 stable disease (33.3%), and 5 disease progression (20.8%). Median overall survival was 18 months and median time-to-progression 5.5 months. This combination showed moderate toxicity and promising antitumor activity in CPT-11 and/or OHP pretreated colorectal cancer patients. The second dose level using CPT-11 at 120 mg/m² and 5-FU at 1800 mg/m² is recommended for further phase II studies in this patient population.     

Effect of 5-Fluorouracil and UFT on Experimental Liver Metastasis Model of Colorectal Cancer Using Mouse Colon 26 Cells

Effects of 5-fluorouracil (5-FU) and UFT on an experimental liver metastasis model were compared at equi-effective dosage levels against subcutaneous tumor of mouse colon 26. 5-FU at the dosage level of 40 mg/kg suppressed the subcutaneous tumor growth by 70.0% and 45.0% on day 13 and day 18, respectively, and UFT at 20 mg/kg provided almost equal suppression (63.0% and 48.0%). In the liver metastasis model, 5-FU at 40 mg/kg showed more potent prevention of the formation of metastatic foci (94.9%) than did UFT (60.4%) at 20 mg/kg. 5-FU at 40 mg/kg produced a much higher peak serum level of 5-FU than did UFT at 20 mg/kg and also showed a much higher AUC (area under the curve) level in the portal blood. These results suggest that oral administration of 5-FU might be useful in prevention of liver metastasis of colorectal cancer.     

Tegafur-Uracil (UFT) Plus Folinic Acid in Advanced Rectal Cancer

We previously reported positive results to Tegafur-Uracil (UFT)chemotherapy in a group of patients with advanced rectal cancer.We have continued the study and now report the effectivenessof UFT plus folinic acid (FA) in 52 patients with advanced rectalcancer. Thetherapeutic schedule was UFT, 600 mg/m²/dayx14 daysp.o. + FA, 90 mg/m2/dayx14 days p.o. Fifty-two out of a totalof 56 patients were evaluated for response and toxicity. A higherincidence of positive responses in patients without previouschemotherapy was appreciated. Twentyone of the 52 evaluatedpatients showed a partial response (PR). Responses were stronglycorrelated with previous chemotherapy (14/20; 70% PR of caseswithout previous chemotherapy vs 7/32; 22% of cases with previouschemotherapy). All responding patients came forward with a mediantime to progression of 8.2 months (19.6 months for patientswithout previous chemotherapy vs 7.7 months for patients withprevious chemotherapy, P>0.01). We concluded that the UFTplus FA could be atreatment of choice for patients with advancedrectal cancer.     

mFOLFOX6方案用于进展期胃癌术后辅助化疗的临床研究

目的观察mFOLFOX6方案用于进展期胃癌术后辅助化疗的临床疗效及不良反应。方法进展期胃癌术后患者29例入mFOLFOX6组,用奥沙利铂85mg/m^2,静脉滴注（〉2h）,第1天;四氢叶酸钙400mg/m^2,静脉滴注（2h）,第1天;氟尿嘧啶0.4g/m^2,静脉推注（四氢叶酸钙之后用）;氟尿嘧啶2.4g/m^2,持续静脉灌注（经化疗泵灌注）46小时。每2周重复1次,2次为1个疗程。同期进展期胃癌术后患者26例入PF组,用顺铂20mg/m^2,静脉滴注,第1～5天;四氢叶酸钙300mg/m^2,静脉滴注（2h）,第1～5天;氟尿嘧啶500mg/m^2,静脉滴注（四氢叶酸钙之后用）,第1～5天;每3周重复1次,为1个疗程。结果mFOLFOX6组和PF组的中位疾病无进展时间分别为8.5个月和6.3个月,有显著性差异,P〈0.05。1年总生存率分别为71%和67%,无显著性差异,P〉0.05,3年总生存率分别为32%和29%,无显著性差异,P〉0.05。mFOLFOX6组恶心呕吐发生率明显低于PF组,P〈0.05。mFOLFOX6组外周神经毒性发生率高于PF组,P〈0.05,但多数为Ⅰ～Ⅱ度。结论mFOLFOX6用于进展期胃癌术后辅助化疗,疾病无进展时间优于旧方案,毒性反应轻,胃癌术后患者容易接受。     

FOLFOX4 方案二线治疗晚期胃癌的临床观察

  目的 评价奥沙利铂联合亚叶酸钙和5氟脲嘧啶组成的FOLFOX4方案二线治疗晚期胃癌的有效性及安全性。方法 34例经过紫杉类药物为主方案治疗后失败的晚期胃癌患者，给予FOLFOX4方案化疗，治疗后按WHO标准进行评价。结果 全组34例，可评价疗效的有33例，其中CR1例，PR6例，SD14例，PD12例，RR率为21．2％，中位缓解时间5个月，中位TTP4．2个月，中位生存期6个月；可评价毒性的有34例，毒副反应主要是骨髓抑制、恶心、呕吐等消化道反应及外周感觉神经毒性，经对症处理，可以逆转。结论 FOLFOX4方案二线治疗晚期胃癌疗效肯定，安全性较好，值得深入研究。