Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-Fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963)

Circadian clocks control cellular proliferation and drug metabolism over the 24?h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N?=?556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p?相似文献   

新辅助化疗与营养支持对老年结肠癌患者T 细胞，COX-2 及tM2-PK水平的影响

目的：探讨新辅助化疗与营养支持综合治疗对老年结肠癌患者血清肿瘤标记物水平、COX-2 及生活质量影响及临床意义。 方法：选取我科收治的老年结肠癌患者80 例,根据治疗方案不同分为对照组与试验组。对照组常规行结肠癌根治切除术,试验组 应用FOLFOX3 方案。比较两组患者血清肿瘤标记物CEA 及CA19-9 水平、COX-2 水平及CD4+、CD8+及tM2-PK 水平。结果：与 治疗前相比,治疗后试验组和对照组CEA 及CA19-9 水平降低（P<0.05),COX-2、tM2-PK 水平降低（P<0.05),CD4+及CD4+/CD8+ 水平降低（P<0.05),CD8+水平升高（P<0.05)。与对照组比较,试验组COX-2、tM2-PK 水平、CD4+、CD8+水平改善明显优于对照组, 差异具有统计学意义（P<0.05),而CEA 及CA19-9 水平组间比较,差异无统计学意义（P>0.05）。结论：新辅助化疗与营养支持综合 治疗可杀伤老年结肠癌患者全身不可见转移肿瘤细胞,控制病情,临床疗效理想。     

Prediction of Survival by Neutropenia According To Delivery Schedule of Oxaliplatin–5-Fluorouracil–Leucovorin for Metastatic Colorectal Cancer in a Randomized International Trial (EORTC 05963)

Circadian clocks control cellular proliferation and drug metabolism over the 24?h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non–time-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N?=?556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p?<?.0001), and G3–4 were 7% and 25%, respectively (p < .0001). Neutropenia was significantly more frequent in women than men on either schedule (FOLFOX2, p = .003; chronoFLO4, p = .04). Median survival was 20.7 mo in patients with G3–4 neutropenia versus 12.5 mo in neutropenia-free patients on FOLFOX2 (p < .0001). Corresponding figures were 13.7 and 19.4 mo, respectively, on chronoFLO4 (p?=?.36). Multivariate analysis confirmed occurrence of severe neutropenia independently predicted for better overall survival on FOLFOX2 (HR?=?0.56; p = .015), and worse survival on chronoFLO4 (HR?=?1.77, p = .06), with a significant interaction test (p < .0001). Prediction of better survival in neutropenic patients on FOLFOX2 supports the administration of conventional chemotherapy near maximum tolerated dose. The opposite trend shown here for chronoFLO4 supports the novel concept of jointly optimized hematologic tolerability and efficacy through personalized circadian-timed therapy. (Author correspondence: francis.levi@inserm.fr)     

SOX 与FOLFOX6 化疗方案治疗老年晚期胃癌患者的临床疗效对比

目的：探讨SOX 与FOLFOX6 化疗方案治疗老年晚期胃癌患者的临床疗效。方法：选择2009 年10 月~2014 年10 月本院收 治的老年晚期胃癌患者共80 例,按照随机数字表法随机分为实验组和对照组,实验组采用SOX 化疗方案,对照组采用FOLFOX6 化疗方案,对两组患者近期有效率、疾病控制率和不良反应发生状况进行评价。结果：两组近期有效率及治疗控制率比较, 差异无统计学意义（P>0.05）。两组患者不良反应主要表现为口腔炎症、胃肠道反应和骨髓抑制,主要以I~II级常见。两组患者口腔 炎、腹泻、白细胞减少、贫血和血小板减少的差异均无统计学意义（P>0.05）,实验组患者恶心呕吐发生率为（19.05%）明显低于对照 组发生率（42.11%）,差异有统计学意义（P<0.05）。结论：SOX和FOLFOX6 化疗方案治疗老年晚期胃癌患者疗效、不良反应发生 状况基本相似,但SOX化疗方案胃肠道副反应更少,且应用方便,值得在临床上推广应用。     

Adjuvant Chemotherapy with Docetaxel,Cisplatin, and Continuous-Infusion 5-Fluorouracil for Gastric Cancer: A Phase II Study

PURPOSE: This study evaluated the efficacy and safety of adjuvant chemotherapy with the docetaxel plus cisplatin and 5-fluorouracil (5-FU) (DCF) regimen in patients with gastric cancer. PATIENTS AND METHODS: Thirty-two patients with gastric or gastroesophageal junction cancer were enrolled in this study after undergoing radical resection. The patients received the following chemotherapy: docetaxel (60 mg/m²) on day 1, cisplatin (12 mg/m² per day) on days 1 to 5, and 5-FU (2500 mg/m²) continuous infusion for 120 hours, repeated every 3 weeks for six cycles. The primary end point was disease-free survival (DFS). RESULTS: The median DFS was 17.0 months. The 1-year DFS was 72%, and the 2-year DFS was 37.5%. The median overall survival was 28.0 months. Using univariate analysis, the technique of lymph node dissection was a predictor for postoperative relapse. The median DFS was 15.0 months in the D1 group and 18.0 months in the D2 group (P = .043). The most frequent grade 3/4 adverse events were neutropenia (56.25%), diarrhea (9.38%), nausea (6.25%), and vomiting (6.25%); 12.5% of patients developed febrile neutropenia. There were no chemotherapy-related deaths. CONCLUSIONS: The modified DCF regimen is an effective adjuvant chemotherapy in gastric cancer. Hematologic toxicity was frequent but manageable. This regimen merits further investigation.     

香砂六君子汤辅助化疗对腹腔镜结肠癌根治术后患者细胞免疫功能和血清肿瘤标志物的影响

摘要 目的：观察香砂六君子汤辅助化疗对腹腔镜结肠癌根治术后患者细胞免疫功能和血清肿瘤标志物的影响。方法：前瞻性选取2019年3月-2021年3月期间来南京医科大学附属江宁医院接受治疗的85例结肠癌患者,均接受腹腔镜结肠癌根治术治疗。分组方法选用随机数字表法,分为对照组（给予化疗治疗,n=42）和研究组（给予香砂六君子汤辅助化疗治疗,n=43）。对比两组疗效、中医证候积分、细胞免疫功能、血清肿瘤标志物和不良反应发生率。结果：与对照组比较,研究组的临床总有效率明显升高（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。研究组治疗结束后CD3⁺、CD4⁺/CD8⁺、CD4⁺高于对照组（P<0.05）。研究组治疗结束后血清癌胚抗原（CEA）、癌抗原125（CA125）、甲胎蛋白（AFP）、CD8⁺水平低于对照组（P<0.05）。研究组治疗结束后腹痛、食少纳呆、腹胀、大便脓血评分低于对照组（P<0.05）。结论：香砂六君子汤辅助化疗治疗腹腔镜结肠癌根治术后患者,可有效促进症状改善,阻止肿瘤细胞扩散,减轻免疫抑制,具有一定的临床价值。     

Evaluation of adjuvant chemotherapy in patients with colorectal cancer in Primorsko-Goranska and Istarska County--a twenty years retrospective study

Colorectal cancer is the second most common malignant disease in developed countries, with about one million new cases worldwide every year, accompanied with high mortality rate. We examined the survival rate and recurrence (occurrence of distant metastases and/or local recurrence) of patients with colorectal cancer in Primorsko-Goranska and Istarska County who received adjuvant chemotherapy, compared to those who did not in the period since 1980. until 1999. This study involves 483 patients with colorectal cancer stages II and III of Primorsko-Goranska and Istarska County, which were underwent curative resections of colorectal cancer at the Clinical Hospital Centre Rijeka, and then treated with chemotherapy (288) or without Chemotherapy (195). We analyzed the five year survival rate and the recurrence of malignant disease in the adjuvant treatment group in comparison with not treated group with chemotherapy, depending on the stage of disease, degree of histological differentiation, patient age and location of cancer (colon or rectum). After follow-up of 60 months died 44.79% (129/288) of patients who received chemotherapy and 53.33% (104/195) of patients who did not receive chemotherapy. The relative risk of death (from any cause) in chemotherapy-treated group versus the group without chemotherapy was 0.82 (p < 0.008). Recurrence of malignant disease in the chemotherapy group was 38.54% (111/288), and in the group without chemotherapy was 46.15% (90/195). The relative risk of recurrence of malignant disease in the chemotherapy group versus the group without chemotherapy was 0.78 (p < 0.001). There was no difference in treatment efficacy regard to the localization of the tumor, but there were differences in efficiency with respect to disease stage, grade and age. Chemotherapy with 5-fluorouracil and leukovorin ameliorate the survival and reduces recurrence and distant metastases in patients with colorectal cancer stages II and III.     

恶性肿瘤化疗所致院内感染31例分析

目的探讨恶性肿瘤患者化疗后发生院内感染的相关因素及防治措施。方法对31例恶性肿瘤患者化疗后发生的院内感染作回顾性分析。结果恶性肿瘤患者化疗后发生院内感染与中性粒细胞减少程度及持续时间有关,感染的部位以呼吸道为主,主要采用粒细胞集落刺激因子（G-CSF）及抗生素治疗。结论恶性肿瘤患者化疗所致院内感染与中性粒细胞减少程度及持续时间密切相关,合理使用G—CSF及抗生素是预防和控制感染的重要措施。     

Elimination of Colon Cancer Stem-Like Cells by the Combination of Curcumin and FOLFOX

5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics but with limited success. This could partly be due to the enrichment of cancer stem cells (CSCs) that are resistant to conventional chemotherapy. Therefore, validation of a nontoxic agent that can either cause reversal of chemoresistance or promote the killing of CSCs would be highly desirable. The current study examines whether curcumin, the major active ingredient of turmeric, either alone or together with FOLFOX, would be an effective strategy to eliminate colon CSCs. Exposure of colon cancer HCT-116 or HT-29 cells to FOLFOX that inhibited their growth led to the enrichment of CSC phenotype as evidenced by increased proportion of CD133-, CD44-, and/or CD166-positive cells and epidermal growth factor receptor (EGFR) levels. Treatment of FOLFOX-surviving colon cancer cells with either curcumin alone or together with FOLFOX resulted in a marked reduction in CSCs, as evidenced by the decreased expression of CD44 and CD166 as well as EGFR and by their ability to form anchorage-dependent colonies. They also caused disintegration of colonospheres. Increased expression of EGFR in FOLFOX-surviving cells could be attributed to hypomethylation of the EGFR promoter, whereas an opposite phenomenon was observed when the FOLFOX-surviving cells were treated with curcumin and/or FOLFOX. These changes were accompanied by parallel alterations in the levels of DNA methyltransferase 1. In conclusion, our data suggest that curcumin by itself or together with the conventional chemotherapeutic could be an effective treatment strategy for preventing the emergence of chemoresistant colon cancer cells by reducing/eliminating CSCs.     

Nonspecific Adverse Events in Knee Osteoarthritis Clinical Trials: A Systematic Review

Background

Adverse events (AEs) derived from nonspecific activity of treatments can impair the validity of trials, and even make it difficult to identify specific AEs associated with treatments. To better understand these nonspecific AEs, we investigated the AEs in placebo groups by using knee osteoarthritis clinical trials.

Methods

Randomized, placebo-controlled, knee osteoarthritis trials were identified by searching electronic databases. We determined the rate of patients with AEs and the rate of dropouts caused by AEs in the active and placebo groups. Furthermore, we calculated the rate of patients for individual AEs in the placebo groups. Finally, we performed secondary analyses to identify the factors associated with these rates.

Results

Overall, 272 papers reporting 281 trials were included in the analysis. The rates of patients with AEs were 31.8% in the active groups and 27.4% in the placebo groups. The rate of the placebo groups accounted for 86.2% of the rate of the active groups. The rates of dropouts caused by AEs were 5.2% in the active groups and 4.8% in the placebo groups. The rate of the placebo groups accounted for 92.3% of the rate of the active groups. AEs in the placebo groups included a number of clinical conditions, with elevated alanine aminotransferase (0.59%; 95% CI: 0.46 to 0.77) being the most common objective outcome and headache (4.48%; 95% CI: 4.20 to 4.79) being the most frequent subjective outcome. The rate of patients with AEs and the rate of dropouts caused by AEs were associated with the treatment type, delivery route, and study design.

Conclusions

The nonspecific AEs substantially accounted for the development of AEs in the active groups and included conditions involving the entire body.     

A phase 2 randomized, double-blind study of AMG 108, a fully human monoclonal antibody to IL-1R, in patients with rheumatoid arthritis

Introduction

Preclinical work has suggested that IL-1 plays a critical role in the pathogenesis of rheumatoid arthritis (RA). The objective of the present study was to determine the effect of a long-acting IL-1 receptor inhibitor, AMG 108, in a double-blind, placebo-controlled, parallel-dosing study in patients with active RA who were receiving stable methotrexate (15 to 25 mg/week).

Methods

Patients were randomized equally to receive placebo or 50, 125, or 250 mg AMG 108 subcutaneously every 4 weeks for 6 months. The primary efficacy endpoint was a 20% improvement in the American College of Rheumatology response (ACR20) at week 24; other efficacy endpoints included the ACR50, the ACR70, and the RA disease activity score (28-joint count Disease Activity Score) responses, patient-reported outcomes, and pharmacokinetic parameters. Safety endpoints included treatment-emergent adverse events (AEs), infectious AEs, serious AEs, serious infections, injection site reactions, laboratory abnormalities, and antibodies to AMG 108.

Results

Of 813 patients enrolled in the study, 204 patients were randomized to the 50 mg group, 203 to the 125 mg group, 203 to the 250 mg group, and 203 to placebo. At week 24, 40.4% of the 250 mg group, 36% of the 125 mg group, 30.9% of the 50 mg group, and 29.1% of the placebo group achieved an ACR20 (P = 0.022, 250 mg vs. placebo). Of the individual ACR components, numerical dose-dependent improvements were only seen in tender joint counts, pain (visual analog scale), and the acute phase reactants, erythrocyte sedimentation rate and C-reactive protein. No dose-related increase was observed in the incidence of treatment-emergent AEs. No deaths were reported, and the incidence of AEs and infections, serious AEs and infections, and withdrawals from study for safety were similar in the AMG 108 and placebo groups.

Conclusions

This large double-blind randomized trial with a long-acting IL-1 receptor blocker, AMG 108, is consistent with the experience of other IL-1 blockers, represents a definitive experiment showing that IL-1 inhibition provides only moderate symptomatic amelioration of arthritis activity in the majority of RA patients, and provides an answer to a question that has been discussed for many years in the rheumatologic community.

Trial Registration

ClinicalTrials.gov NCT00293826     

肠内营养在III期结肠癌术后辅助化疗中的应用价值

目的:探讨肠内营养在Ⅲ期结肠癌术后辅助化疗中的应用价值。方法:对Ⅲ期结肠癌术后辅助化疗的患者常规进行NRS-2002评分,筛选具有营养风险的68例患者,将其随机分为肠内营养联合XELOX方案化疗组及单纯XELOX方案化疗组,对比其消化道副作用、骨髓抑制、神经毒性、手足综合征等化疗副作用的发生情况;体重、血红蛋白、血清白蛋白等营养指标的变化;治疗期间肿瘤复发及转移情况,并评价治疗疗效。结果:肠内营养联合化疗组在化疗期间无肿瘤复发及转移,肠内营养+XELOX组患者恶心呕吐及腹泻的发生率较XELOX组明显降低(P0.05);两组骨髓抑制、神经毒性、手足综合征等副作用均较轻,差异无统计学意义(P0.05)。肠内营养联合化疗组在化疗后血清白蛋白、体重等指数均较化疗前升高,单纯化疗组反而降低;两组间血红蛋白变化无统计学差异(P0.05)。结论:肠内营养在Ⅲ期结肠癌术后有营养风险的辅助化疗患者中具有优越性,可改善患者的营养状态,减轻化疗反应,增强化疗疗效。     

Sodium ditiocarb as adjuvant immunotherapy for high risk breast cancer: A randomized study

Sixty-four patients with non metastatic high risk breast cancer were randomized in a double blind trial of adjuvant immunotherapy with sodium ditiocarb (DDC) versus placebo. All patients underwent prior surgery (mammectomy according to Patey) then adjuvant FAC chemotherapy +/- DDC. With a median follow-up of 5 years we observed 6 relapses and 5 deaths in DDC group; 13 relapses and 12 deaths in control group. At 6 years, overall survival is 81% in DDC group versus 55%. Disease free survival (DFS) is 76% in DDC group versus 55%. DDC associated to chemotherapy and locoregional treatment can improve survival and probably DFS in this high risk breast cancer subgroup.Abbreviations DDC sodium ditiocarb - DFS disease free survival - OS overall survival - N node - FAC 5 Fluorouracil, Adrianycin, Cyclopho-pharmide     

Risk Factors for Severe Neutropenia following Intra-Arterial Chemotherapy for Intra-Ocular Retinoblastoma

Purpose

Intra-arterial chemotherapy is a promising strategy for intra-ocular retinoblastoma. Neutropenia is the most commonly encountered systemic toxicity and in this study we aimed to determine the risk factors associated with the development of severe (≥grade 3) neutropenia.

Methods

Retrospective review of 187 evaluable cycles of melphalan-containing intra-arterial chemotherapy from the first three cycles administered to 106 patients with intra-ocular retinoblastoma from May 2006 to June 2011. Cycles were considered to be evaluable if (1) blood count results were available in the 7 to 14 days post-treatment interval and (2) concurrent intravenous chemotherapy was not administered. Toxicity was assessed via the Common Terminology Criteria for Adverse Events version 4.0.

Results

54 cycles (29%) were associated with grade 3 (n = 43) or grade 4 (n = 11) neutropenia. Multivariate stepwise logistic regression revealed that a higher melphalan dose (>0.40 mg/kg) was significantly associated with severe neutropenia during all 3 cycles (odds ratio during cycle one 4.11, 95% confidence interval 1.33–12.73, p = 0.01), but the addition of topotecan and/or carboplatin were not. Prior treatment with systemic chemotherapy was not associated with severe neutropenia risk in any analysis.

Conclusions

Intra-arterial melphalan-based chemotherapy can cause severe neutropenia, especially when a dose of greater than 0.40 mg/kg is administered. Further study with a larger sample may be warranted.     

Stage III Colon Cancer: The Individualized Strategy of Adjuvant Chemotherapy for Aged Under and Over 70

Background

The aim of this study was to examine the specific chemoregimens selected for adjuvant therapy in the patients with stage III colon cancer. We investigated the trends in chemotherapeutic prescribing patterns and looked for adequate therapeutic setting for these patients.

Methods

288 patients presenting with stage III colon cancer and undergoing adjuvant therapies after curative surgery for more than 3-month were enrolled between January 2006 and December 2011. Demographic characteristics and therapeutic factors were analyzed, including age, gender, histological grade, tumor sizes, tumor location, pathologic stage, performance status, serum carcinoembryonic antigen, regimens selection, interval from the operation to the start of adjuvant therapy and prolonged adjuvant therapy. Kaplan– Meier methods were utilized for drawing survival curves and Cox model was used to analyze survival, prognostic factors.

Results

The analysis showed that the patients aged under 70 received more intensive therapies than those aged over 70 (P<0.001). Later, advanced analysis in therapeutic factors was conducted between the patients aged under 70 and those over 70. In the patients aged under 70, significant differences in 4-year overall survival (OS) were noted between UFUR (oral tegafur-uracil plus leucovorin) groups and FOLFOX (5-FU plus oxaliplatin) [65.6% versus (vs) 89.8%, relative risk (RR) 3.780, 95% confidence interval (CI) 1.263–11.315, P = 0.017]. There were also differences in 4-year OS between these patients with and without oxaliplatin-contained regimens (92.1% vs 83.4%, respectively, RR 0.385, 95% CI 0.157–0.946, P = 0.037). In addition, the patients who received intravenous or combined therapy also had higher 4-year OS than those only received oral regimens (92.1% vs 76.6%, P = 0.077), though the finding did not reach statistical significance. In contrast to the survival benefits of above therapeutic settings for the patients aged under 70, there was less advantage in the old patients when they received intensive therapies or even oxaliplatin-contained regimens. Prolonged cycles of adjuvant therapy resulted in no significant benefit to survival rates regardless of ages.

Conclusions

The adequate individualized therapeutic strategy plays an important role for stage III colon cancer. Our findings suggested that benefit of oxaliplatin-contained therapy is limited to patients aged under 70 and oral fluoropyrimidines may be an effective option for old patients. In addition, prolonged adjuvant setting is suggested to be unbeneficial for managing stage III colon cancer.     

替吉奥治疗结肠癌的研究

目的:探讨替吉奥治疗结肠癌的疗效。方法:75例经病理组织学确诊的结肠癌患者,分为A、B、C组。A组:替吉奥联合奥沙利铂(艾恒)25例。B组:5-Fu/LV联合奥沙利铂(艾恒)25例。C组:替吉奥单药治疗25例。观察疗效、疾病控制率及不良反应。结果:A组、C组与B组对比,不良反应发生率明显降低。A组有效率48%,疾病控制率88%。B组有效率28%,疾病控制率84%。C组有效率32%,疾病控制率80%。结论:替吉奥是结肠癌辅助化疗联合用药及单药治疗老年结直肠癌较好的治疗药物。     

Randomised controlled trial of nicotine chewing-gum.

The effectiveness of 2 mg nicotine chewing-gum as an aid to stopping smoking was compared with a placebo containing 1 mg nicotine, but unbuffered, in a double-blind randomised trial. Of 58 subjects given the active gum, 27 (47%) were not smoking at one-year follow-up compared with 12 (21%) of the 58 subjects treated with placebo (p less than 0.025). By the most stringent criterion of outcome, 18 (31%) subjects in the active treatment group and eight (14%) in the placebo group had not smoked at all from the start of treatment to follow-up at one year (p less than 0.05). Subjects receiving the active gum experienced less severe withdrawal symptoms and rated their gum as more helpful than did the placebo group. Minor side effects were common but only gastric symptoms were more frequent with the active gum. Subjects receiving active gum used it for longer than those receiving placebo but most stopped using it within six months and only four (7%) developed longer-term dependence. The number of gums used daily correlated significantly with pretreatment blood nicotine concentrations in the active treatment group and with pretreatment cigarette consumption in the placebo group. A lower pretreatment blood nicotine value was the best predictor of success at one year (p less than 0.001) but there was no significant relation to cigarette consumption, sex, and social class. The results clearly confirm the usefulness of nicotine chewing-gum as an aid to stopping smoking and imply a definite role for nicotine in cigarette dependence and withdrawal. Successful use of the gum requires careful attention to subjects'' expectations and clear instructions on how to use it.     

FOLFOX4和XELOX两周方案用于进展期胃癌新辅助化疗的随机对照研究

目的:观察FOLFOX4和XELOX新辅助化疗方案治疗局部进展期胃癌的疗效和毒副作用。方法:68例初治确诊为局部进展期胃癌的患者,随机分为两组,每组各34例,分别采用XELOX和FOLFOX4化疗方案行术前两个疗程的化疗治疗。结果:XELOX组总有效率为47.06%,FOLFOX4组总有效率为41.08%,两组间无显著性差异。不良反应方面,FOLFOX4组恶心、呕吐,白细胞减少和口腔黏膜炎发生率较高,而XELOX组手足综合症发生率较高。结论:XELOX方案作为胃癌新辅助化疗方案,疗效与FOLFOX4方案相似,但XELOX方案副作用较轻且均可控制,化疗时间短,对机体损伤小,易于接受,值得在临床工作中进一步研究和推广。     

Weight Loss,HbA1c Reduction,and Tolerability of Cetilistat in a Randomized,Placebo‐controlled Phase 2 Trial in Obese Diabetics: Comparison With Orlistat (Xenical)

The objective of this multicenter, randomized, double‐blind study was to determine the efficacy and safety of cetilistat and orlistat relative to placebo in obese patients with type 2 diabetes, on metformin. Following a 2‐week run‐in, patients were randomized to placebo, cetilistat (40, 80, or 120 mg three times daily), or orlistat 120 mg t.i.d., for 12 weeks. The primary endpoint was absolute change in body weight from baseline. Secondary endpoints included other measures of obesity and glycemic control. Similar reductions in body weight were observed in patients receiving cetilistat 80 or 120 mg t.i.d. or 120 mg t.i.d. orlistat; these reductions were significant vs. placebo (3.85 kg, P = 0.01; 4.32 kg, P = 0.0002; 3.78 kg, P = 0.008). In the 40 mg t.i.d. and placebo groups, reductions were 2.94 kg, P = 0.958 and 2.86 kg, respectively. Statistically significant reductions in glycosylated hemoglobin (HbA_1c) were noted. Cetilistat was well tolerated, and showed fewer discontinuations due to adverse events (AEs) than in the placebo and orlistat groups. Discontinuation in the orlistat group was significantly worse than in the 120 mg cetilistat and placebo groups and was entirely due to gastrointestinal (GI) AEs. Treatment with cetilistat 80 or 120 mg t.i.d., or with orlistat 120 mg t.i.d., significantly reduced body weight and improved glycemic control relative to placebo in obese diabetic patients. Cetilistat was well tolerated with the number of discontinuations due to AEs being similar to placebo.     

A stroma-related lncRNA panel for predicting recurrence and adjuvant chemotherapy benefit in patients with early-stage colon cancer

The heterogeneity in prognoses and chemotherapeutic responses of colon cancer patients with similar clinical features emphasized the necessity for new biomarkers that help to improve the survival prediction and tailor therapies more rationally and precisely. In the present study, we established a s troma-related l ncRNA s ignature (SLS) based on 52 lncRNAs to comprehensively predict clinical outcome. The SLS model could not only distinguish patients with different recurrence and mortality risks through univariate analysis, but also served as an independent factor for relapse-free and overall survival. Compared with the conventionally used TNM stage system, the SLS model clearly possessed higher predictive accuracy. Moreover, the SLS model also effectively screened chemotherapy-responsive patients, as only patients in the low-SLS group could benefit from adjuvant chemotherapy. The following cell infiltration and competing endogenous RNA (ceRNA) network functional analyses further confirmed the association between the SLS model and stromal activation-related biological processes. Additionally, this study also identified three phenotypically distinct colon cancer subtypes that varied in clinical outcome and chemotherapy benefits. In conclusion, our SLS model may be a significant determinant of survival and chemotherapeutic decision-making in colon cancer and may have a strong clinical transformation value.