替吉奥与替吉奥联合顺铂治疗老年进展期胃癌的疗效对比研究

目的观察替吉奥单药与替吉奥联合顺铂治疗老年进展期胃癌的近期疗效、临床受益率和毒副反应。方法 48例老年进展期胃癌患者被随机分入观察组和对照组。观察组24例,患者接受替吉奥胶囊单药口服,连用28 d,停药14 d后再进行下1周期治疗,共完成4周期化疗;对照组24例,采用替吉奥胶囊口服,连用14 d,服药第1～3天给予顺铂静滴化疗,休息7 d后再进行下1周期治疗,用药4周期后评价疗效。结果观察组总有效率为45.8%,临床受益率为91.7%;对照组总有效率为54.2%,临床受益率为66.7%。两组比较近期疗效差异无统计学意义(P>0.05),临床受益率、毒副反应的发生率两组间差异有统计学意义(P<0.05)。结论替吉奥胶囊单药口服治疗老年进展期胃癌可取得较好的近期疗效,可明显提高患者生存质量,耐受性良好。     

替吉奥单药与替吉奥联合顺铂治疗老年晚期胃癌患者的疗效及安全性

目的探讨替吉奥单药与替吉奥联合顺铂治疗老年晚期胃癌患者的疗效及安全性。方法选取2012年1月至2014年7月间安徽医科大学第二附属医院收治的54例老年晚期胃癌患者,采用随机数表法分为单药组(S-1组)28例和联合化疗组(SP组)26例。S-1组患者采用替吉奥治疗,SP组患者采用顺铂联合替吉奥治疗。比较两组患者疗效和化疗后不良反应,采用Kaplan-Meier生存率曲线计算两组患者中位无进展生存时间(PFS)及总生存时间(OS)。结果两组近期疗效、客观缓解率(RR)和疾病控制率(DCR)比较,差异均无统计学意义(均P>0.05)。S-1组患者的中位OS和中位PFS分别为8.6个月和5.0个月,SP组分别为8.9个月及5.5个月,差异均无统计学意义(均P>0.05)。最常见的不良反应是血液学毒性和消化道反应,两组患者总体不良反应比较,差异无统计学意义(P>0.05),无化疗相关性死亡。结论替吉奥单药治疗老年晚期胃癌患者的近期疗效、生存率及安全性与替吉奥联合顺铂的疗效相当,可作为老年晚期胃癌患者的化疗选择。     

替吉奥联合奥沙利铂对比替吉奥联合顺铂方案一线治疗老年晚期胃癌的临床研究

目的 探讨替吉奥联合奥沙利铂方案（SOX）与替吉奥联合顺铂方案（SP）一线治疗老年晚期胃癌的疗效和毒副反应。方法 将56例老年晚期胃癌患者随机分为SOX组（n=30）和SP组（n=26）。SOX组：奥沙利铂130mg／m2 静滴,d1;替吉奥40～60mg／次口服,每天2次,d1～d14,21天为1周期。SP组：顺铂25mg／m2静滴,d1～d3;替吉奥用法同SOX组,21天为1周期。至少2个周期进行疗效评价。结果 SOX组和SP组的有效率分别为46.7％和38.5％（P=0.596）,疾病控制率分别为80.0％和76.9％（P=1.000）;中位无进展生存时间分别为6.0个月和5.6个月（P=0.831）,中位总生存时间分别为12.3个月和11.5个月（P=0.401）。SOX组和SP组的毒副反应均以血液学毒性为主,3～4级发生率的差异无统计学意义;非血液学毒性两组均为1～2级,SOX组以周围神经炎为主,SP组主要为恶心呕吐和肾功能异常。SOX组和SP组的KPS评分提高率分别为83.3％和46.2％（P=0.027）,FACT-G评分提高率分别为76.7％和38.5％（P=0.006）。结论 老年晚期胃癌患者可从替吉奥联合奥沙利铂方案或替吉奥联合顺铂方案一线治疗中获益,但替吉奥联合奥沙利铂方案的毒副反应更小,安全性更好。     

替吉奥联合顺铂治疗晚期胃癌的疗效观察

目的观察替吉奥联合顺铂治疗晚期胃癌的近期疗效和毒副反应。方法 92例晚期胃癌患者随机分为2组,其中替吉奥联合顺铂组49例给予替吉奥联合顺铂治疗,5-氟尿嘧啶联合顺铂组43例给予5-氟尿嘧啶联合顺铂治疗,均21 d为1周期。结果替吉奥联合顺铂组、5-氟尿嘧啶联合顺铂组总有效率分别为59.18%和48.84%,比较差异无统计学意义(P>0.05)。替吉奥联合顺铂组胃肠道反应和口腔黏膜炎发生率分别为59.18%和28.57%,低于对照组的79.07%和51.16%,差异有统计学意义(P<0.05)。结论替吉奥联合顺铂方案是治疗晚期胃癌安全有效的化疗方案。     

替吉奥联合奥沙利铂治疗晚期胃癌临床观察

目的:评价替吉奥联合奥沙利铂治疗晚期胃癌的近期疗效及毒副反应。方法:70例晚期胃癌患者,随机分成对照组与治疗组,每组各35例。治疗组为替吉奥联合奥沙利铂方案,对照组采用奥沙利铂联合亚叶酸钙和5-氟尿嘧啶治疗,2个周期后评价疗效,随访疾病进展时间和总生存期。结果:治疗组总有效率(34.2%)高于对照组总有效率(22.9%),具有统计学意义(P＜0.05)。无疾病进展时间和总生存期治疗组分别为6.8个月和14.0个月,对照组分别为6.6个月和13.5个月,无统计学差异(P＞0.05)。治疗组不良反应发生率明显较对照组低(P＜0.05)。结论:替吉奥胶囊联合奥沙利铂方案治疗晚期胃癌的疗效可靠,毒副作用较轻,不良反应可以耐受,特别适用于年龄较大、一般状态较差的患者。     

替吉奥联合奥沙利铂治疗晚期胃癌的疗效观察和护理

目的 观察替吉奥(S-1)胶囊联合奥沙利铂方案治疗晚期胃癌的临床疗效及毒副反应,及时予以护理干预,使患者顺利完成化疗;方法总结S-1联合奥沙利铂治疗晚期胃癌54例,按RECIST1.1标准评价客观疗效和毒副反应,针对患者出现的化疗毒副反应及护理措施进行详细的记录和分析;结果54例患者均可以评价疗效.CR 4例(7.4%...     

替吉奥胶囊联合奥沙利铂治疗晚期胃癌临床观察

目的 评价替吉奥胶囊联合奥沙利铂治疗晚期胃癌的安全性和有效性.方法 27例晚期胃癌分为两组.试验组14例:替吉奥胶囊80 mg/(m2·d),分2次口服,d1～14;奥沙利铂130 mg/m2,静脉滴注,d1.对照组13例:5-Fu 2400 mg/m2,静脉滴注,d1～5.5;CF0.2,静脉滴注,d1～5;奥沙利铂130 mg/m2,静脉滴注,d1.3周为1个周期.治疗2个周期后评价疗效和毒副反应.结果 试验组总有效率35.7%,对照组30.8%,差异无统计学意义(P＞0.05).两组主要毒副反应均为血液学毒性和消化道反应.结论 替吉奥胶囊联合奥沙利铂治疗晚期胃癌是安全、有效的.     

每周脂质体紫杉醇或奥沙利铂联合替吉奥方案治疗老年晚期胃癌的疗效及安全性分析

目的 比较每周脂质体紫杉醇联合替吉奥与奥沙利铂联合替吉奥一线治疗老年晚期胃癌的疗效及安全性。方法 将119例老年晚期胃癌患者随机分为两组,A组62例患者采用每周脂质体紫杉醇联合替吉奥方案,B组57例患者采用奥沙利铂联合替吉奥方案。比较两组患者的近期疗效、无疾病进展时间（PFS）、总生存时间（OS）、体能状态和不良反应。结果 A组患者的客观缓解率（ORR）、疾病控制率（DCR）、PFS、OS分别为22.0%、69.5%、6.4月和10.8月,B组分别为25.0%、67.9%、6.4月和10.4月,两组间差异均无统计学意义（P均>0.05）。B组Ⅰ~Ⅱ级胃肠道反应、Ⅰ~Ⅱ级和Ⅲ~Ⅳ级外周神经毒性发生率均较A组严重（P均<0.05）。结论 每周脂质体紫杉醇联合替吉奥治疗老年晚期胃癌的近期疗效与传统的奥沙利铂联合替吉奥相似,但前者患者的耐受性更好,可推荐作为老年晚期胃癌患者治疗的首要选择。     

替吉奥联合奥沙利铂治疗晚期胃癌的临床观察

目的 观察替吉奥(S-1)联合奥沙利铂治疗晚期胃癌的近期疗效和毒副反应.方法 33例晚期胃癌均接受化疗:替吉奥胶囊80 mg/(m2·d),早、晚餐后口服,d1～4;奥沙利铂130 mg/m2(2 h静脉滴注),d1;每21 d重复1次,至少2个周期.治疗结束后评价疗效和毒副反应.结果 CR 1例,PR 18例,SD ...     

表柔比星联合奥沙利铂及替吉奥治疗晚期胃癌的近期疗效分析

目的观察表柔比星联合奥沙利铂及替吉奥治疗晚期胃癌的近期疗效及毒副反应。方法 11例经病理确诊的晚期胃癌患者接受化疗:表柔比星70 mg·m-2·d-1,静推,d1;奥沙利铂100 mg·m-2·d-1,静滴,d1;替吉奥80 mg·m-2·d-1,bid,口服,d1～14,每3周为1周期,化疗至少2周期后评价近期疗效和毒副反应。结果 11例患者中,CR 0例(0.00%),PR 5例(45.45%),SD 3例(27.27%),PD 3例(27.27%),有效率为45.45%,疾病控制率为72.73%。毒副反应主要是胃肠道反应、骨髓抑制,发生率分别为81.82%、72.73%,无治疗相关死亡。结论表柔比星联合奥沙利铂及替吉奥治疗晚期胃癌疗效较好,毒副反应可耐受。     

Prediction of S-1-induced anemia

Background  Multiple gastric carcinomas often arise in gastric mucosa with chronic gastritis, particularly severe intestinal metaplasia. In regard to such characteristics, several clinicopathological risk factors for multiple carcinomas have been reported, but no clinically useful criteria are available at present for assessing the onset of multiple gastric carcinomas. If the risk for multiple gastric carcinomas could be accurately assessed, efficient and accurate surveillance could be performed following minimally invasive therapies. Methods  In the present study, we investigated clinicopathological differences between 94 cases of multiple early gastric carcinomas and 285 cases of solitary early gastric carcinoma. We tested 379 specimens of gastric carcinomas that had been surgically resected at the Department of General and Gastroenterological Surgery of Osaka Medical College, Japan, from April 1999 to December 2006. Results  Univariate analysis of clinicopathological factors in the present study showed that multiple gastric carcinomas were significantly correlated to old age (≥65 years), well- and moderately differentiated histological type, mucin phenotype (intestinal type), distribution of atrophic mucosa in the stomach (severe), degree of intestinal metaplasia in the surrounding mucosa (severe), and heterotopic glandular cysts. Multivariate analysis using the stepwise method identified age (≥65 years) and degree of intestinal metaplasia in the surrounding mucosa (severe) as significant independent risk factors for multiple gastric carcinomas. Conclusion  While other studies have shown risk factors for multiple gastric carcinomas, the present study is unique in showing risk assessment criteria based on a combination of risk factors for multiple gastric carcinomas.     

S-1+Low-Dose CDDP

A review of the published literature was undertaken to ascertain the trends in treatment schedules of combination of an oral fluorouracil derivative S-1 with low-dose CDDP (25 mg/m2 or less) for un-resectable and recurrent gastric cancer. The case reports demonstrated as follows: S-1 was given as standard doses of 80-120 mg/body. With regard to CDDP administration, 4 mg/m2 or less was given for 4-consecutive weeks following 2-weeks rest and 6-10 mg/m2 was given for 3-consecutive weeks following 2-weeks rest in the case of 5-day/week CDDP administration. There have been reports of 6-8 mg/m2 CDDP given once or twice a week and weekly CDDP of 10-25 mg/m2 without grade 3 or more adverse events. A phase I study demonstrated the recommend dose of CDDP in the case of 5-day/week was 4 mg/m2 in the regimen of 4-consecutive weeks and 2-weeks rest with a standard dose of S-1. Three phase I studies on weekly low-dose CDDP with S-1 showed the recommend doses were 20-25 mg/m2. S-1+low-dose and a high-dose (30-90 mg/m2) CDDP have come into wide use in Japan. There have been no differences between the case reports and the clinical studies in quantity and quality for both regimens. The unified regimen of S-1+low-dose CDDP as an outpatient based chemotherapy should be developed.     

Prediction of S-1-induced anemia

S-1, a novel oral fluoropyrimidine, has shown remarkably good tolerability in Korean gastric and colorectal cancer patients due to its favorable safety profile. Myelosuppression and diarrhea were the events that precluded dose escalation in Japan, whereas gastrointestinal toxicity and skin reaction were the major limiting factors in Western countries. In contrast, the major adverse event in Korean patients was anemia, which appeared early in the S-1 treatment period and varied among patients. Conventional comparative genomic hybridization (CGH) is used to screen for chromosomal copy number variations such as gene gain, loss, amplification, and deletion. This technique can provide information about genetic instability and chromosomal rearrangements. However, the low resolution of 5–10 Mb is a caveat with conventional CGH. cDNA microarray-based CGH is a useful technique for achieving higher resolution for the detection of genomic aberrations. Pharmacogenomic markers, in combination with clinical factors such as initial hemoglobin level, may be useful for predicting S-1 treatment-induced anemia. Prospective genomic and clinical validation of this model may provide a predictive model for the clinical application of S-1 treatment.     

替吉奥联合奥沙利铂或顺铂治疗进展期胃癌的临床观察

背景与目的:化疗是进展期胃癌主要的治疗手段,但目前尚没有治疗胃癌的标准方案。研究显示替吉奥(S-1)抗肿瘤活性强,患者耐受和依从性好,有望取代氟尿嘧啶(5-FU)成为胃癌化疗方案的核心药物。本研究旨在评估S-1联合奥沙利铂(SOX)和S-1联合顺铂(SP)一线治疗进展期胃癌的疗效和安全性。方法:收集63例SOX和SP方案治疗的进展期胃癌资料进行回顾性分析。根据患者所接受的化疗方案分为两组:SOX组(31例)和SP组(32例)。所有患者均口服S-1 40 mg/m2,每日2次,第1～14天,21 d为1个疗程;SOX组第1天静脉滴注奥沙利铂100 mg/m2;SP组第1天静脉滴注顺铂75 mg/m2。每例患者完成的疗程数为3～8个,平均为4个。结果:所有患者均可评估疗效,SOX组CR 2例(6.5%),PR 14例(45.2%),RR为51.6%。SP组CR 1例(3.1%),PR 16例(50.0%),RR为53.1%,两组的客观有效率差异无统计学意义(P>0.05)。化疗主要不良反应为骨髓抑制、胃肠道反应、乏力、手足综合征和周围神经病变。其中SOX组周围神经病变发生率较SP组高(67.7%vs 12.5%,P<0.05)。结论:SOX和SP化疗方案治疗进展期胃癌均具有较好的近期疗效,且不良反应可以耐受,值得临床进一步研究应用。     

替吉奥联合伊立替康与替吉奥单药治疗晚期结肠癌的临床对照研究

目的比较替吉奥联合伊立替康与替吉奥单药治疗晚期结肠癌的近期疗效、无进展生存时间、总生存时间和不良反应。方法 64例经病理组织学确诊的晚期结肠癌患者随机分为试验组(替吉奥联合伊立替康)和对照组(单药替吉奥)。试验组采用伊立替康150 mg/m2,静脉注射,第1天;替吉奥胶囊80 mg/d(S<1.25 mg/m2),100 mg/d(1.251.5 mg/m2),分2次餐后服用,连用14 d,间隔7 d,每21 d为1个周期。对照组采用替吉奥用法同试验组。至少2个周期评价疗效。用药直到疾病进展或不良反应不能耐受,患者最多接受8个周期治疗。结果试验组的有效率为51.6%,对照组为27.3%,试验组优于对照组(P=0.006)。试验组的疾病控制率为83.9%,对照组为72.7%。64例患者中,56例患者接受随访,中位随访时间为12个月。试验组的中位疾病进展时间为7.0个月(5.6～7.4个月),对照组为4.5个月(4.1～5.5个月),试验组明显优于对照组(P=0.003)。试验组的中位总生存时间为16.5个月(13.4～19.6个月),对照组为13.5个月(8.9～18.0个月),两组患者差异无统计学意义(P>0.05)。主要的不良反应为恶心呕吐、腹泻、贫血和粒细胞减少,对照组患者不良反应轻微;试验组患者恶心呕吐为35.3%,乏力为29.0%,Ⅲ和(或)Ⅳ度粒细胞减少为12.9%,贫血为6.45%,腹泻为12.9%。两组患者腹泻症状比较差异明显(P=0.003),中性粒细胞减少比较差异明显(P=0.011)。结论替吉奥联合伊立替康治疗晚期结肠癌疗效肯定,应药方便,耐受性较好,可做为一线化疗方案的优化,同时也是化疗失败后的二线选择,对不能耐受两药联合化疗的病例,单药替吉奥也值得一线推荐。     

S-1-based therapy versus S-1 monotherapy in advanced gastric cancer: a meta-analysis

This study aimed to derive a more precise estimate of the prognostic significance of S-1-based therapy over S-1 monotherapy in patients with advanced gastric cancer (AGC), including overall survival (OS) time, progression-free survival (PFS) time, objective response rate (ORR), and adverse events (AEs). Studies stratifying OS, PFS, ORR, and AEs in AGC patients in an S-1-based therapy versus an S-1 monotherapy setting were eligible for analysis by systematic computerized PubMed, Embase and Cochrane Library searches. Data from these studies were pooled using STATA package version 11.0. Six studies that investigated outcomes in a total of 913 AGC cases, of which 443 (48.5 %) received S-1-based therapy and 470 (51.5 %) received S-1 monotherapy, were included in the meta-analysis. Median OS and median PFS were significantly prolonged in AGC patients receiving S-1-based therapy compared with those receiving S-1 monotherapy (hazard ratio [HR] 0.83, 95 % confidence interval [CI] 0.71–0.96, P?=?0.015, and HR 0.69, 95 % CI 0.60–0.80, P?=?0.000, respectively). The ORR favored patients with S-1-based therapy (OR 1.65, 95 % CI 1.34–2.06, P?=?0.000). Higher incidence of grade 3/4 neutropenia was found in patients with S-1-based therapy (P?=?0.000). For the Asian population, S-1-based therapy significantly improved OS and PFS and enhanced ORR in comparison to S-1 monotherapy. The safety profile was poorer in patients with S-1-based therapy, but could be considerable between the S-1-based therapy and S-1 monotherapy group. Our conclusion needs to be confirmed via high-quality trials and the results need to be reproduced in other regions and populations.     

S-1 review from preclinical pharmacology

S-1, developed by the scientific theory of both potentiating the antitumor efficacy of 5-fluorouracil (5-FU) and reducing the gastrointestinal (GI) toxicity induced by 5-FU, is a new oral formulation consisting of 1 M tegafur, 0.4 M gimeracil, and 1 M potassium oteracil. By combining gimeracil, a potent inhibitor of 5-FU degradation, and potassium oteracil, which protects against 5-FU-induced GI toxicity to tegafur, S-1, as a dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine (DIF), showed higher antitumor activity, with low intestinal toxicity, compared to continuous infusion of 5-FU (the most effective dosing schedule for 5-FU) and compared to clinically useful oral fluoropyrimidines in various murine and human tumors. In regard to combinations of S-1 with other anticancer drugs, S-1 plus CDDP markedly prolonged survival time in mice suffering gastrointestinal (GI) tumors compared to S-1 in combination with mitomycin-C and/or adriamycin. Furthermore, in combination with irinotecan and taxanes (docetaxel), S-1 exercised synergistic antitumor efficacy not only against 5-FU-sensitive GI cancers with low expression levels of thymidylate synthase (TS) but also against 5-FU-resistant GI tumors with originally elevated levels of TS expression. As one of the reasonable mechanisms of anticancer synergism exerted by an S-1 combination, irinotecan and docetaxel were found to downregulate the expression of TS in gastric cancers. Throughout our pharmacological studies of S-1, alone and in combination with other anticancer drugs, we found that S-1 could be expected to contribute greatly to the treatment of patients with gastric cancer.     

S-1 review from preclinical pharmacology

S-1, developed by the scientific theory of both potentiating the antitumor efficacy of 5-fluorouracil (5-FU) and reducing the gastrointestinal (GI) toxicity induced by 5-FU, is a new oral formulation consisting of 1 M tegafur, 0.4 M gimeracil, and 1 M potassium oteracil. By combining gimeracil, a potent inhibitor of 5-FU degradation, and potassium oteracil, which protects against 5-FU-induced GI toxicity to tegafur, S-1, as a dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine (DIF), showed higher antitumor activity, with low intestinal toxicity, compared to continuous infusion of 5-FU (the most effective dosing schedule for 5-FU) and compared to clinically useful oral fluoropyrimidines in various murine and human tumors. In regard to combinations of S-1 with other anticancer drugs, S-1 plus CDDP markedly prolonged survival time in mice suffering gastrointestinal (GI) tumors compared to S-1 in combination with mitomycin-C and/or adriamycin. Furthermore, in combination with irinotecan and taxanes (docetaxel), S-1 exercised synergistic antitumor efficacy not only against 5-FU-sensitive GI cancers with low expression levels of thymidylate synthase (TS) but also against 5-FU-resistant GI tumors with originally elevated levels of TS expression. As one of the reasonable mechanisms of anticancer synergism exerted by an S-1 combination, irinotecan and docetaxel were found to downregulate the expression of TS in gastric cancers. Throughout our pharmacological studies of S-1, alone and in combination with other anticancer drugs, we found that S-1 could be expected to contribute greatly to the treatment of patients with gastric cancer.     

S-1 monotherapy for pancreatic cancer

Early and late phase II studies of S-1 were conducted for the treatment of metastatic pancreatic cancer. In both trials, S-1 was administered at a dose of 80 mg/m2/day. One course consisted of consecutive administration of S-1 for 28 days, followed by 14 days of rest. This regimen was repeated every 6 weeks until the occurrence of progressive disease or unacceptable toxicities. The early phase II study demonstrated a response rate of 21.1% with a median survival time of 5.6 months in 19 patients. The major drug-related adverse events were gastrointestinal toxicities like nausea, and anorexia, though most of them were tolerable and reversible. Other treatment-related adverse events, like ileus, colitis, and abdominal distension, were less frequent. The late phase II study confirmed favorable responces with a mild toxicity profile in 40 evaluable patients. S-1 is active and well tolerated in patients with metastatic pancreatic cancer. Randomized trials are warranted to determine the effectiveness of S-1 for the treatment of pancreatic cancer.