奥沙利铂联合氟尿嘧啶与亚叶酸钙术前化疗诱导胃癌细胞早期凋亡的研究

观察奥沙利铂联合氟尿嘧啶、亚叶酸钙诱导胃癌细胞早期凋亡的效果。胃癌患者17例，术前1周应用奥沙利铂联合氟尿嘧啶、亚叶酸钙化疗(治疗组)，术中取胃癌组织，应用流式细胞术(AV与P1双参数法)检测其凋亡；并与18例术前未化疗(对照组)的胃癌患者进行比较。术前化疗组胃癌细胞凋亡比例为28．53％明显高于术前未化疗组的13．59％ P＜0．05。奥沙利铂联合氟尿嘧啶、亚叶酸钙化疗可通过促进胃癌细胞凋亡而发挥其抗胃癌作用。     

奥沙利铂在治疗晚期胃肠道肿瘤中的应用

目的 观察奥沙利铂联合氟尿嘧啶亚叶酸钙治疗晚期胃肠道肿瘤的疗效、不良反应及探索合适的给药方式.方法将30例胃癌病例、33例结肠癌病例、32例直肠癌病例随机分为氟尿嘧啶亚叶酸钙联合顺铂组(对照组)、氟尿嘧啶亚叶酸钙联合单次大剂量奥沙利铂治疗组(处理组1)及氟尿嘧啶亚叶酸钙联合分次小剂量奥沙利铂治疗组(处理组2).各组中,化疗药物用法分别为:对照组:CF 100 mg/m2d1～5,5-Fu 350 mg/m2d1～5,DDP 25 mg/m2d1～3;处理组1:CF 100 mg/m2d1～5,5-Fu 350 mg/m2d1～5,L-OHP 100 mg/m2d1;处理组2:CF 100 mg/m2d1～5,5-Fu 350 mg/m2d1～5,L-OHP 35 mg/m2d1～4,均21天重复,使用4～6周期后评价疗效及不良反应.结果奥沙利铂联合氟尿嘧啶亚叶酸钙治疗晚期胃癌、结肠癌、直肠癌的有效率分别可达40%±、55%±、50%±.奥沙利铂分次给药较单次给药的疗效相同但毒副作用明显降低.结论奥沙利铂分次给药联合氟尿嘧啶亚叶酸钙是治疗晚期胃肠道肿瘤的毒性小、有效率高的方案.     

紫杉醇联合氟尿嘧啶治疗青年进展期胃癌疗效观察

目的:观察紫杉醇联合氟尿嘧啶治疗青年进展期胃癌的临床疗效及不良反应。方法:86例经病理学证实青年Ⅲ-Ⅳ期胃癌患者,随机分为2组:紫杉醇组40例予紫杉醇联合亚叶酸钙及氟尿嘧啶,铂类组予奥沙利铂联合亚叶酸钙及氟尿嘧啶方案化疗,均化疗2个周期以上,每个周期28d。结果:紫杉醇组有效率50%,有末梢神经炎、血液学毒性,胃肠道反应率为25%。含奥沙利铂方案的有效率48%,有末梢神经炎、血液学毒性,胃肠道反应率为44%。2组有效率比较无显著性差异(P>0.05),胃肠道反应率比较有显著性差异(P<0.05)。结论:紫杉醇联合亚叶酸钙及氟尿嘧啶治疗青年进展期胃癌不良反应小,尤其是胃肠道不良反应较小,疗效确切,甚至可以代替铂类做为一线方案首选。     

奥沙利铂、紫杉醇分别联合5-氟脲嘧啶或亚叶酸钙治疗晚期胃癌的临床对照研究

目的比较奥沙利铂、紫杉醇分别联合5-氟脲嘧啶/亚叶酸钙组成的两组联合化疗方案治疗晚期胃癌的疗效与不良反应。方法84例患者分为A、B两组。A组43例，采用奥沙利铂联合5-氟脲嘧啶或亚叶酸钙治疗，B组41例，采用紫杉醇联合5-氟尿嘧啶或亚叶酸钙治疗。两组方案均以21天为1个周期，化疗至少2个周期。结果A组患者有效率、中位肿瘤进展时间、中位生存期、1年生存率分别是51.2%、5.9个月、9.3个月、28.1%，B组则分别是46.3%、6.1个月、9.1个月、26.5%。两组有效率与生存期比较无显著性差异（P〉0.05）。两组主要毒副反应为骨髓抑制，恶心呕吐，但不严重。结论奥沙利铂、紫杉醇分别联合5-氟脲嘧啶或亚叶酸钙治疗晚期胃癌，有较好疗效，且疗效相似，毒副反应均可耐受。     

雷替曲塞联合奥沙利铂化疗治疗晚期大肠癌的临床观察

目的 探讨雷替曲塞联合奥沙利铂化疗治疗晚期大肠癌的疗效,以期为一线化疗方案失败的晚期大肠癌患者提供治疗方案.方法 将48例晚期大肠癌患者随机分为对照组和观察组,对照组进行奥沙利铂联合5-氟尿嘧啶及亚叶酸钙方案化疗,观察组进行雷替曲塞联合奥沙利铂化疗.对2组患者的近期疗效、不良反应发生率进行比较.结果 观察组患者治疗有效率明显高于对照组,白细胞减少、血小板减少、恶心、呕吐等不良反应的发生率明显低于对照组,差异均有统计学意义(P＜0.05).结论 雷替曲塞联合奥沙利铂治疗晚期大肠癌的临床疗效优于奥沙利铂联合5-氟尿嘧啶及亚叶酸钙化疗治疗,且不良反应发生率低.     

紫杉醇联合氟尿嘧啶治疗青年进展期胃癌疗效观察

目的：观察紫杉醇联合氟尿嘧啶治疗青年进展期胃癌的临床疗效及不良反应。方法：86例经病理学证实青年Ⅲ-Ⅳ期胃癌患者,随机分为2组：紫杉醇组40例予紫杉醇联合亚叶酸钙及氟尿嘧啶,铂类组予奥沙利铂联合亚叶酸钙及氟尿嘧啶方案化疗,均化疗2个周期以上,每个周期28d。结果：紫杉醇组有效率50%,有末梢神经炎、血液学毒性,胃肠道反应率为25%。含奥沙利铂方案的有效率48%,有末梢神经炎、血液学毒性,胃肠道反应率为44%。2组有效率比较无显著性差异（P〉0.05）,胃肠道反应率比较有显著性差异（P〈0.05）。结论：紫杉醇联合亚叶酸钙及氟尿嘧啶治疗青年进展期胃癌不良反应小,尤其是胃肠道不良反应较小,疗效确切,甚至可以代替铂类做为一线方案首选。     

奥沙利铂、羟基喜树碱、氟尿嘧啶、亚叶酸钙联合方案治疗晚期胃癌42例

[目的]评价奥沙利铂、羟基喜树碱、氟尿嘧啶、亚叶酸钙联合治疗42例晚期胃癌疗效.[方法]羟基喜树碱10mg/m2静滴第1～5d,奥沙利铂100mg/m2静滴第1d;亚叶酸钙100 mg/d静滴第6～10d,氟脲嘧啶750 mg/d静滴第6～10d.28天为1个化疗周期,完成3周期后评价疗效.[结果]42例晚期胃癌患者中CR 3例(7.14%),PR 17例(40.48%),NC 14例(40.48%),PD 8例(33.33%).总有效率(CR PR)为47.62%(20/42).毒副反应为骨髓系和消化系不良反应,发生率较高,基本上为Ⅰ度和Ⅱ度.经对症处理后均能缓解.本组未发生严重不良反应而终止治疗者,也无与化疗相关死亡病例.[结论]奥沙利铂、羟基喜树碱、氟尿嘧啶、亚叶酸钙治疗晚期胃癌疗效好,毒副反应轻.     

奥沙利铂联合亚叶酸钙和氟尿嘧啶治疗大肠癌肝转移40例近期疗效观察

目的观察奥沙利铂联合亚叶酸钙和氟尿嘧啶治疗大肠癌肝转移患者的近期疗效及不良反应。方法对40例患者应用奥沙利铂 亚叶酸钙 氟尿嘧啶联合治疗2周期,评价疗效。结果有效率(CR PR)37.5%,不良反应少,外周神经毒性可以耐受且可逆。结论奥沙利铂联合亚叶酸钙和氟尿嘧啶是一种安全、有效的治疗晚期大肠癌的药物。     

奥沙利铂联合氟尿嘧啶及亚叶酸钙治疗晚期胃癌的临床研究

目的观察奥沙利铂联合氟尿嘧啶及亚叶酸钙治疗晚期胃癌的疗效和不良反应。方法采用奥沙利钔130mg／m^2，静滴2h，第1天；亚叶酸钙（CF）200mg／m^2，静滴, 连续5天；5-Fu 500mg/m^2静滴4h，连续5天，21天为1周期。结果35例患者中CR 1例，PR 13例，总有效率40．0％。 主要的不良反应为消化道症状、骨髓抑制和感觉神经毒性。结论奥沙利铂联合氟尿嘧啶及亚叶酸钙治疗晚期胃癌疗效肯定，毒副作用较轻，值得推广应用。     

雷替曲塞联合奥沙利铂与5-氟尿嘧啶和亚叶酸钙联合奥沙利铂方案治疗晚期结直肠癌疗效的比较

目的探讨雷替曲塞联合奥沙利铂与5-氟尿嘧啶和亚叶酸钙联合奥沙利铂方案治疗晚期结直肠癌的疗效及不良反应。方法选择2010年6月至2014年1月间收治的经病理学明确诊断的126例晚期结直肠癌患者,按随机数字表法分为治疗组和对照组,每组各63例。治疗组患者采用雷替曲塞联合奥沙利铂方案治疗,对照组患者采用5-氟尿嘧啶和亚叶酸钙联合奥沙利铂方案治疗。观察两组患者的临床疗效和不良反应等方面的差异。结果治疗组患者完全缓解0例,部分缓解22例,稳定23例,进展18例,总有效率为34.9%(22/63);对照组患者完全缓解0例,部分缓解20例,稳定23例,进展20例,总有效率为31.7%(20/63),两组患者的总有效率比较差异无统计学意义(P>0.05)。两组患者均有骨髓抑制发生,以I、Ⅱ度为主;治疗组患者恶性呕吐、腹泻和黏膜炎的发生率低于对照组,差异有统计学意义(P<0.05);两组患者均未出现严重的肝、肾、心脏毒性,无治疗相关性死亡。结论雷替曲塞联合奥沙利铂方案治疗晚期结直肠癌的疗效与5-氟尿嘧啶和亚叶酸钙联合奥沙利铂方案疗效相当,但不良反应较轻,值得临床广泛应用。     

国产草酸铂联合氟尿嘧啶及甲酰四氢叶酸钙治疗胃肠癌近期疗效分析

目的 :观察国产草酸铂 (L OHP)联合氟尿嘧啶 (5 FU)、甲酰四氢叶酸钙 (CF)治疗晚期胃癌、大肠癌的疗效。方法 :LFP方案L OHP 130mg m2 ,静脉滴入 ,d1 ;CF 10 0mg m2 ,静脉滴入 ,d1 ～d5;5 FU5 0 0mg m2 ,静脉滴入 ,4～ 6h ,d1 ～d5(5 FU后用 ) ,2 1d为 1个周期。结果 :全组CR 1例 ,PR 12例 ,SD14例 ,PD 5例 ,总有效率 4 0 6 %。初治有效率 4 5 4 % ,复治有效率 38 1% ;胃癌与大肠癌有效率分别为4 1 7%和 37 5 %。主要不良反应为消化道反应及外周神经毒性。结论 :L OHP联合 5 FU、CF方案疗效肯定 ,经济实用 ,毒性可耐受     

3DRT辅助卡培他滨与奥沙利铂化疗方案对进展期胃癌术后生存研究

目的 探讨三维适形调强放疗联合奥沙利铂+卡培他滨化疗治疗进展期胃癌对其术后中位生存时间的影响。方法 自临沂市中心医院2010年2月至2012年1月选取进展期胃癌患者中选取74例,根据治疗方案分为术后化疗组(37例)与术后放化疗组(37例)。两组均采用腹腔镜D2根治术,术后化疗组采用奥沙利铂联合卡培他滨化疗,术后放化疗组采用奥沙利铂联合卡培他滨化疗+三维适形调强放疗,两组均化疗4个周期。疗程结束后统计对比两组不良反应发生情况、中位无进展生存时间、中位生存时间、治疗后1、3、5年疾病复发率及病死率。结果 术后放化疗组骨髓抑制率(41%)、肝功能异常率(30%)、呕吐恶心率(30%)、白细胞减少率(46%)与术后化疗组(35%、35%、24%、41%)相比,差异无统计学意义(P>0.05)。术后放化疗组中位无进展生存时间、中位生存时间较术后化疗组长,差异有统计学意义(P<0.05)。两组治疗后1、3、5年疾病复发率比较,术后放化疗组(8%、14%、16%)较术后化疗组(32%、41%、46%)低,差异有统计学意义(P<0.05);术后放化疗组病死率11%(4/37)较术后化疗组30%(11/37)低,差异有统计学意义(P<0.05)。结论 三维适形调强放疗联合奥沙利铂+卡培他滨化疗治疗进展期胃癌,可有效延长患者中位生存时间,降低疾病复发率,且不会增加不良反应发生风险。     

ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen

Molecular markers involved in DNA repair can help to predict survival in gastric cancer patients treated with 5-FU plus platinum chemotherapy. Excision repair cross-complementing 1 (ERCC1) and thymidylate synthase (TS) mRNA expression levels were assessed in advanced gastric cancer tumour samples using real-time quantitative PCR in 76 patients treated with a modified FOLFOX (biweekly oxaliplatin plus 5-FU and folinic acid) regimen. Median survival time in patients with low ERCC1 levels was significantly longer than in those with high levels (15.8 vs 6.2 months; P<0.0001). Patients with high TS levels had longer survival than those with low levels (12.2 vs 10.1 months; P=0.01). Forty-eight patients with low ERCC1 and high TS levels had a median survival of 16.1 months (P<0.0001). The hazard ratio for patients with high ERCC1 expression was 9.4 (P<0.0001). In patients with high mRNA levels of ERCC1, alternative chemotherapy regimens should be considered.     

奥沙利铂联合氟尿嘧啶２周方案与３周方案一线治疗进展期胃癌的比较研究

目的　比较奥沙利铂（Ｌ-ＯＨＰ）联合氟尿嘧啶／亚叶酸钙（５-ＦＵ／ＣＦ）的２周方案与３周方案一线治疗进展期胃癌的临床疗效及不良反应。方法　８８例进展期胃癌患者,其中２周方案组４８例,具体方案：Ｌ-ＯＨＰ８５ｍｇ／ｍ２静脉滴注２小时,第１天;ＣＦ２００ｍｇ／ｍ２静脉滴注２小时,第１、２天;５-ＦＵ４００ｍｇ／ｍ２静脉推注,６００ｍｇ／ｍ２持续静脉滴注２２小时,第１、２天,２周重复１次,２次计为ｌ周期,２周期评价疗效。３周方案组４０例,具体方案：Ｌ-ＯＨＰ１３０ｍｇ／ｍ２ 静脉滴注２小时,第１天;ＣＦ２００ｍｇ／ｍ２静脉滴注２小时,第１～５天;５-ＦＵ３７５ｍｇ／ｍ２静脉滴注６小时,第１～５天,３周重复１次,每次计为１周期,２周期评价疗效。结果　全组均可评价疗效,２周方案及３周方案的ＲＲ分别为４７.９％和４５.０％（Ｐ＞０.0５）,中位肿瘤进展时间（ＴＴＰ）分别为９.０个月和６.６个月（Ｐ＜０.０５）,中位总生存期（ＯＳ）分别为１３.６个月和１０.０个月（Ｐ＜０.０５）。两组主要毒副反应为消化道反应,神经系统、血液学毒性和脱发,发生率近似。结论　Ｌ-ＯＨＰ联合５-ＦＵ／ＬＶ２周方案与３周方案的近期疗效和安全性无差异,但远期疗效较优,值得临床进一步研究。     

Treatment of Advanced Gastric Carcinoma Patients with Calcium Folinate, a 5-Fluorouracil Bolus and Continous Infusion with 5-Infusion with 5-Fluorouracil Combined with Oxaliplatin

OBJECTIVE To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil (5-FU) bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin (L-HOP)in treating advanced gastric carcinoma patients.METHODS Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin. The effects of treatment and toxicity were observed.RESULTS There were 4 complete responses, 26 partial responses,30 with no change and 5 with progressive disease. The overall effective response rate was 46.2% (30/65). The median duration was 7 months, with the main side effects including nausea and vomiting, peripheral phlebitis, alopecia, leukopenia, dental ulcers,peripheral neuritis and diarrhea. All the side effects were tolerated and minimal.CONCLUSION The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma. This therapeutic regimen is of value for these patients.     

Mismatch repair status is a predictive factor of tumour response to 5-fluorouracil and irinotecan chemotherapy in patients with advanced colorectal cancer.

BACKGROUND AND AIMS: To determine the association between DNA mismatch repair (MMR) protein expression and response to chemotherapy in patients with advanced colorectal cancer (CRC). METHODS: Using immunohistochemistry, tumour expression of 2 MMR genes, hMLH1 and hMSH2, was assessed in 86 patients with advanced CRC, who were treated with either irinotecan alone or in combination with 5-flurouracil/folinic acid. RESULTS: Weak/negative staining in the tumours was associated with the presence of metastases at diagnosis (p = 0.026) and with the time for metastases to appear (p = 0.0001). An objective response to treatment was observed in 32/56 (57%) patients who had tumours with negative/weak MMR protein expression (p = 0.001), compared to 17% of patients with tumours with moderate/strong expression. Those who had tumours with weak/absent expression of either hMLH1 or hMSH2 who received the combination therapy were more likely to show an objective response (p = 0.0001). CONCLUSION: Advanced CRC patients whose tumours have deficient MMR demonstrate a shorter time to metastasis than those with normal hMLH1/hMSH2 expression. Patients with MMR-deficient tumours are also more likely to benefit from combination chemotherapy (irinotecan plus 5-flurouracil/folinic acid).     

Treatment of advanced gastric carcinoma patients with calcium folinate, a 5-fluorouracil bolus and continous infusion with 5-fluorouracil combined with oxaliplatin

Objective  To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil (5-FU) bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin (L-HOP)in treating advanced gastric carcinoma patients. Methods  Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin. The effects of treatment and toxicity were observed. Results  There were 4 complete responses, 26 partial responses, 30 with no change and 5 with progressive disease. The overall effective response rate was 46.2% (30/65). The median duration was 7 months, with the main side effects including nausea and vomiting, peripheral phlebitis, alopecia, leukopenia, dental ulcers, peripheral neuritis and diarrhea. All the side effects were tolerated and minimal. Conclusion  The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma. This therapeutic regimen is of value for these patients.     

大剂量醛氢叶酸加 5-FU持续 48小时滴注为主方案治疗晚期胃癌的初步研究

目的：评价大剂量醛氢叶酸加5－氟尿嘧啶（5－fluorouracil,5-FU)持续48h滴注为主方案治晚期胃癌的客观疗效及不良反应,探索晚期胃癌较合理的治疗方案。方法：对入选的31例晚期胃癌病人采用大剂量醛氢叶酸＋5－FU持续48h滴注为主方案进行治疗,平均2．55个疗程。结果：完全缓解（complete remission,CR)2例,部分缓解（partial remission,PR)14例,稳定（no change,NC)12例,进展（progressive disease,PD)3例,有效率为51．61％,主要的不良反应为恶心呕吐、口腔粘膜炎、骨髓抑制、脱发及腹泻。上述不良反应除恶心呕吐较明显外,其余绝大多数为Ⅰ-Ⅱ度,且发生率不高,经常规对症治疗后见好转。结论：大剂量醛氢叶酸＋5－FU持续48h滴注为主方案治疗晚期胃癌疗效好,不良反应轻。     

A pilot phase II study of chemotherapy with oxaliplatin, folinic acid, 5-fluorouracil and irinotecan in metastatic gastric cancer

AIMS AND BACKGROUND: Previous phase II studies have reported that combinations of oxaliplatin, folinic acid and 5-fluorouracil or irinotecan, folinic acid and 5-fluorouracil are associated with good efficacy and an acceptable safety profile in metastatic gastric cancer. The aim of this study was to evaluate chemotherapy with oxaliplatin, folinic acid, 5-fluorouracil and irinotecan (COFFI regimen) in metastatic gastric cancer. METHODS: Patients received oxaliplatin (85 mg/m2 d 1), irinotecan (140 mg/m2 d 1), and L-folinic acid (200 mg/m2 d 1) followed by 5-fluorouracil bolus (400 mg/m2 d 1) and then 5-fluorouracil (2,400 mg/m2 48-h continuous infusion), every 14 days. RESULTS: Seventeen patients with metastatic gastric cancer were enrolled. Eight patients were pretreated for advanced disease. Of the 9 chemo-na?ve patients, 8 were evaluated for response (1 patient was lost to follow-up): one complete response, 5 partial responses and 2 progressions of disease occurred, giving an overall response rate, at intention-to-treat analysis, of 67%. Of the 8 pretreated patients, 6 were evaluated for response (2 patients had nonmeasurable disease): one partial response, 2 disease stabilizations and 3 progressions of disease occurred, giving an overall response rate, at intention-to-treat analysis, of 12%. Median progression-free and overall survival in chemo-na?ve patients were 8.2 and 10.2 months, respectively, and in pretreated patients 2.7 and 3 months. Grade 3-4 neutropenia occurred in 55% of chemo-na?ve patients. Thrombocytopenia, and anemia were observed in 18% and 29%, respectively. Grade 3 nausea/vomiting occurred in 12% and grade 3 diarrhea in 6%. CONCLUSIONS: The COFFI regimen is active and well tolerated, therefore phase III studies are warranted.     

草酸铂联合卡培他滨治疗晚期胃癌的近期疗效分析

目的：探讨草酸铂联合卡培他滨治疗晚期胃癌的近期疗效。方法：对32例晚期胃癌采用草酸铂联合卡培他滨方案治疗共76周期。结果：CR6例，PR16例，NC8例和PD2例，总有效率(CR PR)为68．75％(22／32)。中位缓解期8个月，中位生存期12个月，1年生存率为55％；临床受益者共30例(93．75％)。不良反应可耐受，经积极对症治疗后均见好转，无相关死亡出现。无患者因为不良反应中止治疗。结论：草酸铂加卡培他滨方案而组成的OX方案治疗晚期胃癌疗效较好，毒性反应能够耐受，可作为经济状况好的患者的一线方案在更多的病人中应用，以进一步探讨其疗效。