Neoadjuvant intraperitoneal and systemic paclitaxel combined with apatinib and S-1 chemotherapy for conversion therapy in gastric cancer patients with positive exfoliative cytology: a prospective study

BackgroundTo explore the efficacy and safety of neoadjuvant intraperitoneal and systemic (NIPS) paclitaxel chemotherapy combined with apatinib and S-1 in the treatment of gastric cancer patients with positive exfoliative cytology.MethodsPatients with gastric cancer (P₀CY₁) who were confirmed to have free cancer cells (FCCs) in the abdominal cavity after laparoscopic exploration from April 2018 to August 2019 were enrolled. All patients underwent NIPS chemotherapy using paclitaxel combined with apatinib and S-1 treatment. Laparoscopic exploration was performed after 3 cycles of conversion therapy. The primary study endpoint was the FCC negative rate, and the secondary study endpoints were overall survival time (OS), progression-free survival time (PFS), objective response rate (ORR), disease control rate (DCR), and safety indicators.ResultsOut of 312 advanced gastric cancer patients who underwent laparoscopic exploration, 36 patients with P₀CY₁ gastric cancer were identified and enrolled in this study. After 3 cycles of conversion therapy, the ORR was 80.56% and the DCR was 94.44%. All patients underwent secondary laparoscopic exploration, and the FCC conversion rate was 77.78%. All patients with negative FCC underwent R0 surgical resection, with a median follow-up time of 11.4 months. The median survival time was 15.5 months, and the 1-year OS was 80.55%. The median PFS was 14.4 months, and the 1-year PFS was 75.00%. Treatment-related grade 3 adverse reactions were mainly leukopenia and neutropenia. No grade 4 adverse reactions were observed. There were no reported deaths related to chemotherapy or surgery in the study cohort.ConclusionsNIPS with paclitaxel combined with apatinib and S-1 treatment may increase the FCC negative rate of P₀CY₁ gastric cancer patients.     

替吉奥联合紫杉醇或奥沙利铂治疗进展期胃癌的临床观察

目的 观察替吉奥（S-1）联合紫杉醇或奥沙利铂一线治疗进展期胃癌的临床疗效和不良 反应。方法 91例进展期胃癌患者分为替吉奥联合奥沙利铂(SOX组)和紫杉醇(PS组)方案化疗,其 中SOX组44 例,PS组47例。所有患者S-1均是80 mg/m2,分2次餐后口服,d1~d14;SOX组：奥沙 利铂 130 mg/m2,d1,静脉滴注;PS组：紫杉醇 80 mg/m2,d1、8,静脉滴注。均21天为1周期。结 果 SOX组和PS组的有效率分别为36.4%和40.4%(P=0.691),两组的中位无疾病进展时间(5.0月 vs. 5.4 月,P=0.45)和中位生存时间(13.5月 vs. 16.4月,P=0.76)无显著差异。SOX组和PS组的不良反应主要 是中性粒细胞减少、胃肠道反应、乏力;SOX组和PS组的恶心、呕吐发生率分别为79.5％和51.1％(P ＜0.05)。结论 替吉奥联合紫杉醇或奥沙利铂治疗进展期胃癌有效率和生存期相当,均有较好的疗 效,不良反应可以耐受。     

奥沙利铂联合紫杉醇脂质体治疗晚期胃癌的疗效分析

目的 探讨奥沙利铂联合紫杉醇脂质体或替吉奥治疗晚期胃癌的临床疗效及不良反应.方法 选取46例晚期胃癌患者作为研究对象.按照随机数字表法将46例晚期胃癌患者随机分为A组和B组,每组23例.其中,A组患者接受奥沙利铂联合紫杉醇脂质体方案化疗,B组患者接受奥沙利铂联合替吉奥方案化疗.比较两组患者的客观缓解率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS)和不良反应发生情况.结果 A组患者的ORR为47.8%,DCR为78.3%;B组患者的ORR为43.5%,DCR为69.6%;两组患者的ORR和DCR比较,差异均无统计学意义(P=0.767、0.502).A组和B组患者的中位OS分别为9.4个月和9.5个月,两组比较,差异无统计学意义(P=0.911).A组患者的中位PFS为6.9个月(95%CI:6.2~7.8个月),长于B组患者的5.4个月(95%CI:4.0~5.9个月),差异有统计学意义(P=0.048).两组患者的中性粒细胞减少、血小板减少、贫血、疲劳乏力、腹泻、关节肌肉疼痛、恶心呕吐以及神经毒性的发生率比较,差异均无统计学意义(P﹥0.05).结论 奥沙利铂联合紫杉醇脂质体方案和奥沙利铂联合替吉奥方案治疗晚期胃癌的临床疗效接近,但在晚期胃癌患者的无进展生存期方面,奥沙利铂联合紫杉醇脂质体方案可能优于奥沙利铂联合替吉奥方案.     

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.     

白蛋白结合型紫杉醇联合替吉奥一线治疗老年晚期胰腺癌患者的临床观察

目的:探讨白蛋白结合型紫杉醇联合替吉奥方案一线治疗老年晚期胰腺癌患者的疗效及安全性。方法:回顾性分析2014年10月至2016年10月解放军总医院28例接受白蛋白结合型紫杉醇联合替吉奥方案一线化疗的晚期转移性胰腺癌老年患者(年龄≥60岁)的临床资料。根据NCI-CTC3.0标准每周期评价不良反应,依据实体肿瘤RECIST标准每2周期评估疗效,并随访其生存情况。结果:接受白蛋白结合型紫杉醇联合替吉奥方案一线化疗的28例患者的ORR为42.9%（12/28）,DCR为82.1%（23/28）。接受治疗的28例患者的中位PFS为9.4个月(95%CI:6.1～12.7个月),中位OS为12.6个月（95%CI:7.6～17.5个月）。不良反应发生情况:白细胞减少（71.4%）、恶心呕吐（53.6%）、脱发（46.4%）、感觉神经异常（53.6%）。Ⅲ-Ⅳ度不良反应包括白细胞减少（21.4%）、脱发（3.6%）、口腔黏膜炎（3.6%）、感觉神经异常（3.6%）。结论:白蛋白结合型紫杉醇联合替吉奥方案一线治疗老年晚期胰腺癌疗效较好,不良反应可耐受。     

Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer

Background:

A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting.

Methods:

Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m⁻² twice daily) on days 1–14 plus paclitaxel (60 mg m⁻²) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m⁻² twice daily) on days 1–21 plus cisplatin (60 mg m⁻²) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety.

Results:

A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7% P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin.

Conclusion:

S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials.     

替吉奥联合奥沙利铂方案与紫杉醇联合奥沙利铂和5-氟尿嘧啶方案治疗晚期胃癌的疗效对比

目的探讨替吉奥联合奥沙利铂方案(SOX方案)和紫杉醇联合奥沙利铂和5-氟尿嘧啶方案(POF方案)治疗晚期胃癌的疗效和不良反应。方法收集2010年2月至2013年6月间晚期胃癌患者48例,分为SOX组和POF组,分别采用SOX方案(23例)和POF方案(25例)。至少完成2个周期化疗,比较两组患者的疗效和不良反应。结果 SOX组患者的有效率(RR)为47.8%,疾病控制率(DCR)为65.2%;POF组患者的RR为44.0%,DCR为68.0%,两组差异均无统计学意义(均P>0.05)。SOX组患者的中位疾病进展时间(TTP)为7.2个月,中位总生存期(OS)为11.5个月;POF组患者的TTP为8.4个月,OS为12.3个月,两组差异均无统计学意义(均P>0.05)。两组患者的不良反应也相似,以Ⅰ^Ⅱ级的血液学毒性和消化道反应为主。SOX组患者的血小板减少发生率高于POF组(P<0.05),POF组患者脱发发生率高于SOX组(P<0.05)。结论 SOX方案治疗晚期胃癌疗效与POF方案相似,耐受性好,应用更方便。     

白蛋白结合型紫杉醇联合替吉奥治疗晚期胰腺癌的研究进展

胰腺癌早期症状隐匿,恶性程度高,是消化系统常见的恶性肿瘤之一。外科手术是延长胰腺癌患者生存期的最佳选择,但只有15%~20%的胰腺癌患者能接受手术治疗。其余患者因局部晚期或全身转移,只能进行以内科治疗为主的综合治疗。目前晚期胰腺癌患者的首选治疗方式是以吉西他滨为基础的化疗,但仅使晚期胰腺癌患者的平均生存期延长为5.5~7个月,疗效有限。近几年,多项研究证实白蛋白结合型紫杉醇联合替吉奥治疗晚期胰腺癌可以提高患者的PFS和OS（分别为6.2个月和13.6个月）。治疗过程中最常出现的不良反应是中性粒细胞减少,但未出现因不良反应而停止治疗或死亡的现象。为晚期胰腺癌患者的治疗带来了新希望。本文将总结白蛋白结合型紫杉醇联合替吉奥在治疗晚期胰腺癌中的相关研究。     

进展期胃癌S-1与5-FU基础化疗有效性和安全性Meta分析

目的 S-1被应用于进展期胃癌一线化疗中,其疗效也备受关注.本研究评估S-1基础化疗对比5-氟尿嘧啶(5-Fluorouracil,5-FU)基础化疗方案在进展期胃癌一线化疗中的有效性和安全性.方法 用“胃癌、替吉奥或S-1、5-氟尿嘧啶和随机对照研究”等检索词,在Pubmed、Embase、Cochrane Library、ASCO会议摘要、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)和中文科技期刊全文数据库(VIP)等检索相关的临床随机对照试验,检索时间截止至2016-10.提取总生存期、无疾病进展生存期、有效率、3～4级不良反应等数据.采用Revman 5.3和STATA 12.0进行数据分析.结果 共纳入18个随机对照研究,3 581例患者.结果显示,S-1基础化疗在总生存期(HR=0.92,95％CI为0.84～1.01,P=0.07)及无疾病进展生存期(HR=0.90,95％CI为0.76～1.07,P=0.25)方面与5-FU基础化疗方案差异无统计学意义,但有更高的有效率,RR=1.46,95％CI为1.22～1.74,P＜0.001.S-1基础化疗方案3～4级中性粒细胞减少(P＜0.001)、白细胞减少(P＜0.001)、血小板减少(P=0.01)、口腔炎(P＜0.001)和脱发(P=0.02)等不良反应较5-FU基础化疗发病率更低,差异有统计学意义.结论 相比于5-FU基础化疗,S-1基础化疗在进展期胃癌一线治疗中均是有效且更安全的化疗方案.     

A retrospective study of S-1 and oxaliplatin combination chemotherapy in patients with refractory pancreatic cancer

Purpose

The aim of this study was to evaluate S-1 and oxaliplatin combination chemotherapy (SOX) in patients with refractory pancreatic cancer (PC).

Methods

Consecutive patients with advanced PC refractory to gemcitabine who were treated with oral S-1 (80 mg/m²) on days 1–14 and intravenous oxaliplatin (100 mg/m²) on day 1 every 3 weeks were studied retrospectively. The primary end point was the objective response rate (ORR). The secondary end points were progression-free survival (PFS), overall survival (OS), the disease control rate (DCR), and safety.

Results

Between March 2009 and October 2011, 30 patients were treated with SOX, with a median of two courses (range 1–8). The ORR and DCR were 10.0 and 50.0 %, respectively. Median PFS and OS were 3.4 months (95 % confidence interval [CI] 1.3–5.3) and 5.0 months (95 % CI 3.4–7.4), respectively. The median PFS and OS were 5.6 and 9.1 months in patients receiving S-1 and oxaliplatin as a second-line treatment. Major grade 3 or 4 adverse events included neutropenia (10.0 %), anemia (3.3 %), and diarrhea (6.7 %).

Conclusions

SOX was well tolerated and moderately effective in patients with refractory PC.     

Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701)

BackgroundLentinan (LNT) is a purified β-1, 3-glucan that augments immune responses. The present study was conducted to assess the efficacy of LNT in combination with S-1 as a first-line treatment for unresectable or recurrent gastric cancer.Patients and methodsEligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment.ResultsOne hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group.ConclusionsOS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer.Clinical trial registration ID numberUMIN 000000574.     

A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer

BackgroundWe evaluated the efficacy and toxicity of adding oral leucovorin (LV) to S-1 when compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer (PC).Patients and methodsGemcitabine-refractory PC patients were randomly assigned in a 1:1 ratio to receive S-1 at 40, 50, or 60 mg according to body surface area plus LV 25 mg, both given orally twice daily for 1 week, repeated every 2 weeks (SL group), or S-1 monotherapy at the same dose as the SL group for 4 weeks, repeated every 6 weeks (S-1 group). The primary end point was progression-free survival (PFS).ResultsAmong 142 patients enrolled, 140 were eligible for efficacy assessment (SL: n = 69 and S-1: n = 71). PFS was significantly longer in the SL group than in the S-1 group [median PFS, 3.8 versus 2.7 months; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37–0.85; P = 0.003]). The disease control rate was significantly higher in the SL group than in the S-1 group (91% versus 72%; P = 0.004). Overall survival (OS) was similar in both groups (median OS, 6.3 versus 6.1 months; HR, 0.82; 95% CI, 0.54–1.22; P = 0.463). After adjusting for patient background factors in a multivariate analysis, OS tended to be better in the SL group (HR, 0.71; 95% CI, 0.47–1.07; P = 0.099). Both treatments were well tolerated, although gastrointestinal toxicities were slightly more severe in the SL group.ConclusionThe addition of LV to S-1 significantly improved PFS in patients with gemcitabine-refractory advanced PC, and a phase III trial has been initiated in a similar setting.Clinical trials numberJapan Pharmaceutical Information Center: JapicCTI-111554.     

Randomized phase II study comparing paclitaxel with S-1 vs. S-1 as first-line treatment in patients with advanced gastric cancer

Purpose

This randomized phase II study was conducted to compare the efficacy and safety of paclitaxel with S-1 (PS) vs. S-1 in patients with advanced gastric cancer (AGC).

Methods

Eighty-two (82) patients were 1:1 randomly assigned to oral S-1 (daily for 2 weeks, every 4 weeks’ cycle) or S-1 (daily for 2 weeks, every 4 weeks’ cycle) plus paclitaxel (on day 1, 8 and 15 of a 4 weeks’ cycle). S-1 was orally administered with a fixed quantity according to body surface area (BSA), while paclitaxel was given 60 mg/m² i.v. daily through an implanted catheter. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall responsible rates and safety.

Results

The median OS with PS versus S-1 monotherapy was 14.0 versus 11.0 months (P = 0.02), survival at 12 months was 61.0 % in the PS group and 46.3 % in the S-1 group. Median PFS was also significantly longer in the PS group (6.0 months) than in the S-1 group (4.0 months). The overall response rate was determined in 82 evaluable patients, and was significantly higher (P = 0.04) with PS (19 patients, 46.3 %) than with S-1 monotherapy (10 patients, 24.4 %). PS was well tolerated with no treatment-related deaths, all were grade 3–4 gastrointestinal toxicities, including anorexia, nausea, and diarrhea developed in less than 10 % of the patients.

Conclusions

Combination chemotherapy of paclitaxel with S-1 is well tolerated and active in AGC patients. Further investigation with comparative trials is needed for confirmation.     

A multicentre randomised trial comparing weekly paclitaxel + S-1 with weekly paclitaxel + 5-fluorouracil for patients with advanced gastric cancer

PurposeThis study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).MethodsPatients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm’s dosage schedule was paclitaxel 60 mg/m² (intravenous infusion) on days 1, 8 and 15 and S-1 80–120 mg/d (oral administration) on days 1–14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m² (continuous intravenous infusion) on days 1–5; and leucovorin 20 mg/m² (intravenous infusion) on days 1–5. All schedules were repeated every 28 d.ResultsA total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473–0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705–2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3–4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.ConclusionWeekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.     

Randomised phase II trial of S-1 plus oxaliplatin vs S-1 in patients with gemcitabine-refractory pancreatic cancer

Background:

This randomised, open-label, multicenter phase II study compared progression-free survival (PFS) of S-1 plus oxaliplatin (SOX) with that of S-1 alone in patients with gemcitabine-refractory pancreatic cancer.

Methods:

Patients with confirmed progressive disease following the first-line treatment with a gemcitabine-based regimen were randomised to receive either S-1 (80/100/120 mg day⁻¹ based on body surface area (BSA), orally, days 1–28, every 6 weeks) or SOX (S-1 80/100/120 mg day⁻¹ based on BSA, orally, days 1–14, plus oxaliplatin 100 mg m⁻², intravenously, day 1, every 3 weeks). The primary end point was PFS.

Results:

Between January 2009 and July 2010, 271 patients were randomly allocated to either S-1 (n=135) or SOX (n=136). Median PFS for S-1 and SOX were 2.8 and 3.0 months, respectively (hazard ratio (HR)=0.84; 95% confidence interval (CI), 0.65–1.08; stratified log-rank test P=0.18). Median overall survival (OS) was 6.9 vs 7.4 months (HR=1.03; 95% CI, 0.79–1.34; stratified log-rank test P=0.82). The response rate (RR) was 11.5% vs 20.9% (P=0.04). The major grade 3/4 toxicities (S-1 and SOX) were neutropenia (11.4% and 8.1%), thrombocytopenia (4.5% and 10.3%) and anorexia (12.9% and 14.7%).

Conclusions:

Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone.     

A phase II study of combination therapy with oral S-1 and cisplatin in elderly patients with advanced gastric cancer

Background

A combination of S-1 and cisplatin is recognized as one of the standard first-line chemotherapy regimens for patients with advanced gastric cancer. However, demographic analyses of pivotal phase III studies have showed that only a minority of treated patients were aged 76 years or older. The purpose of this phase II study was to evaluate the safety and efficacy of combination therapy with S-1 and cisplatin in elderly patients with chemotherapy-naive advanced gastric cancer.

Methods

Patients aged 76 years or older received S-1 40 mg/m² orally twice daily for 21 days and cisplatin 60 mg/m² intravenously infused at day 8 of each 35-day cycle. Dose modification was performed according to creatinine clearance. The primary endpoint was overall survival (OS). Secondary endpoints included response rate, progression-free survival (PFS), time to treatment failure (TTF), and adverse events.

Results

A total of 40 patients were enrolled. Median OS was 12.3 months, PFS was 7.8 months, and TTF was 4.3 months. The response rate was 54%. The most common grade 3–4 adverse events were anorexia (25%), neutropenia (23%), hyponatremia (20%), anemia (18%), and febrile neutropenia (8%). No treatment-related death occurred.

Conclusions

Combination chemotherapy with S-1 and cisplatin is an effective and well-tolerated regimen for elderly patients with advanced gastric cancer when the dose is adjusted according to renal function.

     

多西他赛、奥沙利铂联合替吉奥（DOS）与奥沙利铂联合替吉奥(SOX)治疗晚期胃癌的临床观察

目的:观察多西他赛、奥沙利铂联合替吉奥(DOS)与替吉奥联合奥沙利铂(SOX)方案一线治疗晚期胃癌的近期疗效和安全性。方法:回顾性分析71例晚期胃癌患者,根据患者所接受的化疗方案分为DOS组(36例)和SOX组(35例)。DOS组:多西他赛60mg/m2静脉滴注1h,第1天;奥沙利铂100mg/m2静脉滴注3h,第1天;替吉奥胶囊(S-1)30mg/m2,口服,每日2次,第1-14天,每21天为1个周期。SOX组:奥沙利铂130mg/m2静脉滴注3h,第1天;替吉奥40mg/m2,口服,每日2次,第1-14天,每21天为1个周期。连用2个周期后评价疗效和每个周期观察不良反应。结果:所有患者均可评估疗效,DOS组CR 1例(2.8%),PR 16例(44.4%),SD 10例（27.8%）,有效率（RR）为47.2%,疾病控制率（DCR）为75.0%,中位无进展生存期(PFS)4.4个月。SOX组CR患者0例,PR 15例(42.9%),SD 13例（37.1%）,有效率为42.9%,疾病控制率为80%,中位无进展生存期4.0个月。两组的客观有效率、疾病控制率及中位无进展生存期差异均无统计学意义(P>0.05)。化疗主要不良反应为骨髓抑制、胃肠道反应、脱发和周围神经病变。其中,脱发发生率DOS组显著高于SOX组(P<0.001);I/II级周围神经毒性,SOX组发生率显著高于DOS组(P=0.005）。结论:DOS和SOX化疗方案治疗进展期胃癌疗效相近,不良反应均可耐受。     

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。     

The clinical efficacy of cytotoxic agents in locally advanced or metastatic breast cancer patients pretreated with an anthracycline and a taxane: A systematic review

IntroductionCurrently available evidence does not provide definitive guidance regarding the optimal chemotherapy agents and combinations in anthracycline- and taxane-pretreated advanced breast cancer. We performed a systematic review of controlled clinical trials of the cytotoxic agents currently used for this population in Europe: capecitabine, gemcitabine, vinorelbine, docetaxel, paclitaxel and paclitaxel protein-bound particles.MethodA systematic review of randomised (RCT) and non-randomised controlled clinical trials (non-RCTs). The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS); secondary outcomes were duration of response (DR), overall response rate (ORR), adverse events and quality of life (QoL). Six electronic databases and grey literature sources were searched; reference tracking was performed on included publications. A narrative synthesis was conducted: heterogeneity of study design and interventions prevented meta-analysis.ResultsNo randomised controlled trial (RCT) found any significant differences between any of the regimens in terms of OS. In terms of PFS, only gemcitabine plus vinorelbine performed significantly better than its comparator, vinorelbine alone. For secondary outcomes, only capecitabine plus bevacizumab had a significantly better outcome than its comparator, capecitabine alone, in terms of ORR. A low quality non-RCT found that both capecitabine monotherapy and a combination of capecitabine plus vinorelbine were significantly more effective than vinorelbine alone in terms of OS and ORR. Across all trials, median OS for these patients typically remained less than 16 months.ConclusionThe quantity and quality of the available evidence regarding the efficacy of the particular chemotherapy regimens in patients with advanced breast cancer pretreated with an anthracycline and a taxane is extremely limited. New effective therapies are sorely needed in this population.     

Randomised phase II study of S-1/cisplatin plus TSU-68 vs S-1/cisplatin in patients with advanced gastric cancer

Background:

This study aimed to determine whether combination S-1 plus cisplatin (CDDP) therapy, the most widely used therapy for Japanese patients with advanced gastric cancer, and the novel oral antiangiogenic agent TSU-68 could contribute to gastric cancer treatment.

Methods:

Ninety-three patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers were randomised into two groups: TSU-68 plus S-1/CDDP (group A) and S-1/CDDP (group B) groups. Both patient groups received identical S-1 and CDDP dosages. TSU-68 was orally administered for 35 consecutive days. Group B patients received S-1 orally twice daily for three consecutive weeks, followed by intravenous CDDP on day 8. The primary endpoint was progression-free survival (PFS).

Results:

Median PFS periods were 208 and 213 days in groups A and B, respectively (P=0.427). Median survival periods for groups A and B were 497.0 and 463.5 days, respectively (P=0.219). No statistically significant differences were noted for PFS, survival or the adverse event (AE) incidence rate. All AEs were expected according to previous reports for TSU-68, TS-1, and CDDP.

Conclusion:

Combination therapy involving TSU-68, S-1, and CDDP was safe and well tolerated in patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers. However, factors related to therapeutic efficacy should be investigated further.