卡培他滨与氟尿嘧啶/亚叶酸钙联合奥沙利铂治疗晚期胃癌的随机对照临床研究

背景与目的：目前对进展期及转移性胃癌还没有标准的化疗方案,而且缺乏有效率高、毒副反应小、安全的化疗方案.毒副反应是晚期胃癌化疗的限制性因素,影响患者的生活质量.本研究观察及比较两种常用化疗方案卡培他滨联合奥沙利铂方案（XELOX）与氟尿嘧啶/亚叶酸钙联合奥沙利铂方案（FOLFOX4）治疗晚期胃癌的临床疗效及毒副反应,以期取得在较佳疗效保证的同时,毒副反应小,耐受性更好的效果.方法：48例晚期胃癌患者随机分成两组,XELOX组与FOLFOX4组.XELOX组25例,用卡培他滨联合奥沙利铂方案化疗,卡培他滨1000 mg/m^2,口服,2次/日,第1～14天;奥沙利铂130 mg/m^2,静脉点滴,第l天;2l d为1个周期.FOLFOX4组23例,用氟尿嘧啶/亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85 mg/m^2,静脉点滴,第1天;亚叶酸钙200 mg/m^2,静滴2 h后予氟尿嘧啶400 mg/m^2,推注,后续600 mg/m^2持续静滴22 h,第1、2天;每2周重复,4周为1周期.两组均治疗2周期以上.按wH0标准评价客观疗效和毒副反应.结果：入组48例均可评价疗效,XELOX组有效率56.0%,中位TTP 5.8个月,MST 10个月,FOLFOX4组有效率47.8%,中位TTP 5.7个月,MST 9.8个月.两组近期有效率差异无显著性.毒副反应比较,手足综合征以：XELOX组显著（P＜0.05）,Ⅲ/Ⅳ级恶心呕吐发生率以FOLFOX4.组显著（P＜0.05）,其余毒副反应除腹泻外发生率以FOIFOX4组稍高,但差异无显著性.结论：XELOX方案与FOLFOX4方案治疗晚期胃癌疗效确切,毒副反应能耐受.两组近期疗效相似,毒副反应以XELOX组更易耐受,尤其对一般情况欠佳及老年的患者耐受性好.     

XELOX方案与FOLFOX4方案治疗转移性结直肠癌的临床观察

目的:观察两种常用化疗方案卡培他滨联合奥沙利铂方案(XELOX)与5-氟尿嘧啶/亚叶酸钙联合奥沙利铂方案(FOLFOX4)治疗转移性结直肠癌的临床疗效及不良反应.方法:48例晚期结直肠癌患者随机分成两组,XELOX组与FOLFOX4组.XELOX组25例,予卡培他滨联合奥沙利铂方案化疗,卡培他滨1000mg/m2,口服,2次/日,第1-14天;奥沙利铂130mg/m2,静脉点滴,第1天;21天1周期.FOLFOX4组23例,予5-氟尿嘧啶,亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85mg/m2,静脉点滴,第1天;亚叶酸钙200mg/m2,静滴2小时后予5-氟尿嘧啶400mg/m2,推注,后续600mg/m2持续静滴22小时,第1、2天;每2周重复,4周为1周期.两组均治疗2周期以上.按WHO标准评价客观疗效和不良反应.结果:48例均可评价疗效,XELOX组有效率48.0%(CR 2,PR 10),中位TTP 7.1个月,MST 13.8个月,FOLFOX4组有效率47.8%(CR 2,PR 9),中位TTP 7.3个月,MST 14.0个月.两组近期有效率无明显统计学差异.不良反应比较,手足综合征以XELOX组显著(P<0.05),Ⅲ-Ⅳ级恶心呕吐发生率FOLFOX4组高(P<0.05),余不良反应除腹泻外发生率以FOLFOX4组稍高,但无统计学意义.结论:XELOX方案与FOLFOX4方案治疗晚期结直肠癌疗效确切,不良反应能耐受.两组近期疗效相似,不良反应XELOX组更低.     

XELOX方案与FOLFOX4方案治疗转移性结直肠癌的临床观察

目的：观察两种常用化疗方案卡培他滨联合奥沙利铂方案（XELOX）与5-氟尿嘧啶/亚叶酸钙联合奥沙利铂方案（FOLFOX4）治疗转移性结直肠癌的临床疗效及不良反应。方法：48例晚期结直肠癌患者随机分成两组,XELOX组与FOLFOX4组。XELOX组25例,予卡培他滨联合奥沙利铂方案化疗,卡培他滨1000mg／m^2,口服,2次／日,第1—14天;奥沙利铂130mg／m^2,静脉点滴,第1天;21天1周期。FOLFOX4组23例,予5-氟尿嘧啶,亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85mg／m^2,静脉点滴,第1天;亚叶酸钙200mg／m^2,静滴2小时后予5-氟尿嘧啶400mg／m^2,推注,后续600mg／m^2持续静滴22小时,第1、2天;每2周重复,4周为1周期。两组均治疗2周期以上。按WHO标准评价客观疗效和不良反应。结果：48例均可评价疗效,XELOX组有效率48．0％（CR2,PR10）,中位TTP 7．1个月,MST 13．8个月,FOLFOX4组有效率47．8％（CR2,PR9）,中位TTP 7．3个月,MST 14．0个月。两组近期有效率无明显统计学差异。不良反应比较,手足综合征以XELOX组显著（P〈0．05）,Ⅲ-Ⅳ级恶心呕吐发生率FOLFOX4组高（P〈0．05）,余不良反应除腹泻外发生率以FOLFOX4组稍高,但无统计学意义。结论：XELOX方案与FOLFOX4方案治疗晚期结直肠癌疗效确切,不良反应能耐受。两组近期疗效相似,不良反应XELOX组更低。     

奥沙利铂为主方案治疗进展期结直肠癌的临床观察

目的：观察含奥沙利铂联合方案治疗进展期结直肠癌的临床疗效及毒副反应.方法：经病理检查确诊的36例进展期结直肠癌患者分为A、B两组,分别予FOLFOX4（奥沙利铂、氟尿嘧啶和亚叶酸钙）方案及XELOX（奥沙利铂和卡培他滨）方案化疗,按WHO标准评价客观疗效和毒副反应.结果：入组36例均可评价疗效.A组24例,无CR者,PR9例,近期客观有效率37.5%,中位疾病进展时间（TTP）为7.0个月;B组12例,CR1例,PR4例,近期客观有效率41.7%,中位TTP为7.1个月,两组近期有效率无统计学差异.结论：与标准的FOLFOX4方案比较,XELOX方案治疗进展期结直肠癌疗效确切,毒副反应轻,尤其对于一般情况欠佳的患者耐受性好.     

贝伐珠单抗联合奥沙利铂+卡培他滨化疗治疗转移性结直肠癌的疗效及安全性

目的 探讨贝伐珠单抗联合奥沙利铂+卡培他滨化疗治疗转移性结直肠癌的疗效及安全性.方法 采用随机数字表法将78例转移性结直肠癌患者分为对照组和研究组,每组39例,对照组患者给予奥沙利铂+卡培他滨化疗,研究组患者给予贝伐珠单抗联合奥沙利铂+卡培他滨治疗.治疗2个疗程后,比较两组患者的临床疗效、肿瘤标志物[癌胚抗原(CEA)...     

卡培他滨联合奥沙利铂与5-氟尿嘧啶亚叶酸钙联合奥沙利铂在Ⅲ期结直肠癌辅助化疗中的疗效和安全性比较

目的 比较卡培他滨联合奥沙利铂(XELOX方案)与5-氟尿嘧啶+亚叶酸钙联合奥沙利铂(FOLFOX4方案)在Ⅲ期结直肠癌辅助化疗中的疗效和安全性.方法 回顾性分析118例Ⅲ期结直肠癌患者的临床资料,其中76例应用FOLFOX4方案治疗,42例应用XELOX方案治疗,比较两组患者的3年无病生存率(DFS)和不良反应的发生率.结果 FOLFOX4组未完成8个周期化疗的患者有28例,XELOX组有8例,差异有统计学意义(P=0.044).FOLFOX4组患者的3年DFS为72.4%,XELOX组为73.8%,差异无统计学意义(P=0.866).FOLFOX4组和XELOX组患者各种常见不良反应的总发生率差异并无统计学意义(均P>0.05),但在3～4度不良反应中,FOLFOX4组患者中性粒细胞减少的发生率高于XELOX组(P<0.05),而XELOX组患者血小板减少和手足综合征的发生率高于FOLFOX4组(均P<0.05).结论 XELOX方案与FOLFOX4方案作为Ⅲ期结直肠癌辅助化疗的疗效相同,但XELOX方案的耐受性更好.     

XELOX方案治疗晚期结直肠癌临床观察

目的比较卡培他滨(希罗达)联合奥沙利铂(XELOX)方案与亚叶酸钙、氟尿嘧啶(5-Fu)联合奥沙利铂(FOLFOX4)方案一线治疗晚期转移性结直肠癌的疗效和不良反应。方法将56例晚期结直肠癌患者随机分为两组,XELOX方案组(28例):卡培他滨(capecitabine,Xeloda)1000mg/m2,Bid,口服,d1~14;奥沙利铂(oxaliplatin)130mg/m2,静脉滴注,持续2h,d1;21 d为1周期。FOLFOX4方案组(28例):奥沙利铂85 mg/m2,静脉点滴2 h,d1;醛氢叶酸200 mg/m2,静脉点滴2 h,d1、2;氟尿嘧啶400 mg/m2,莫非氏管静脉推注d1、2;氟尿嘧啶600 mg/m2,静脉持续滴注(化疗泵),持续22 h,d1、2,14 d为1周期。结果 XELOX组总有效率(RR)50.0%,中位肿瘤进展时间(TTP)7.0个月;FOLFOX4组RR为46.4%,TTP为6.8个月;两组比较各项指标差异无显著性(P>0.05)。不良反应中XELOX组手足综合征发生率高于FOLFOX4组,Ⅲ、Ⅳ度中性粒细胞减少发生率低于FOLFOX4组。结论 XELOX方案一线治疗晚期结直肠癌有确切疗效,不良反应可耐受,与FOL-FOX4方案相当,但XELOX方案用药更为方便,安全性更好。     

XELOX与FOLFOX6应用于晚期结直肠癌治疗的临床观察

目的探讨卡培他滨+奥沙利铂(XELOX)化疗方案与亚叶酸钙/5-氟脲嘧啶+奥沙利铂(FOLFOX6)化疗方案治疗晚期结直肠癌的近期疗效、不良反应及远期生存率的影响。方法选取106例晚期结直肠癌患者为研究对象,其中接受XELOX化疗方案者57例,接受FOLFOX6方案者49例。对比2组治疗总疗效、不良反应发生情况以及生存率。结果治疗后,XELOX组总有效率为56.14%,FOLFOX6组总有效率为53.06%,2组差异无统计学意义(P>0.05)。XELOX化疗组手足综合征发生率为14.04%,明显高于FOLFOX6化疗组发生率2.04%,差异有统计学意义(P<0.05),但其程度较轻,主要以Ⅰ~Ⅱ度为主;FOLFOX6化疗组神经毒性发生率为22.45%,明显高于XELOX化疗组发生率5.26%(P<0.05),程度较轻,主要以Ⅰ~Ⅱ度为主;2组在白细胞减少、恶心、呕吐、口腔炎、脱发等发生率上比较,差异无统计学意义(P>0.05)。XELOX组疾病无进展生存时间中位数为15个月,FOLFOX6组17个月;XELOX化疗组1年生存率为85.96%,高于FOLFOX6化疗组1年生存率83.67%,但差异无统计学意义(P>0.05)。结论 XELOX与FOLFOX6化疗方案治疗晚期结直肠癌的疗效相当,但XELOX化疗方案用药更为安全方便。     

奥沙利铂加卡培他滨经肝动脉化疗栓塞术治疗结直肠癌肝转移

目的观察奥沙利铂加卡培他滨经肝动脉化疗栓塞术治疗结直肠癌肝转移的临床效果和毒副反应。方法入组70例结直肠癌术后多发性肝转移患者,根据治疗方案的不同分为2组,观察组35例给予奥沙利铂加卡培他滨经肝动脉化疗栓塞术治疗,对照组35例给予常规奥沙利铂加卡培他滨方案(静脉给药)。结果观察组、对照组有效率分别为68.6%、37.2%,差异有统计学意义(P<0.05);中位生存期分别为14.6、10.8个月,比较差异无统计学意义(P>0.05)。观察组神经毒性、骨髓抑制发生率低于对照组,差异有统计学意义(P<0.05)。结论奥沙利铂加卡培他滨经肝动脉化疗栓塞术治疗结直肠癌肝转移疗效和耐受性均优于奥沙利铂加卡培他滨常规静脉给药。     

XELOX与FOLFOX6方案一线治疗晚期结直肠癌的近期疗效及不良反应比较

目的：比较卡培他滨（希罗达）联合奥沙利铂（XELOX）方案与亚叶酸钙、5-氟尿嘧啶（5-FU）联合奥沙利铂（FOLFOX6）方案一线治疗晚期转移性结、直肠癌的疗效和不良反应。方法：将62例晚期结、直肠癌患者随机分为两组,XELOX方案组（n=31）：卡培他滨（capecitabine,Xeloda）1000mg／m^2,2次／d,口服,第1天至第14天;奥沙利铂（oxaliplatin）130mg／m^2,静脉滴注,持续3h,第1天;21天为1周期。FOLFOX6方案组（n=31）：亚叶酸钙（CF）200mg／m^2,静脉滴注,第1天,5-FU前;5-FU400mg／m^2,静脉推注,第1天,2400mg／m^2,静脉持续滴注46h;奥沙利铂100mg／m^2,静脉滴注,持续3h,第1天;14天为1周期。结果：XELOX组缓解率（RR）为48．4％,中位肿瘤进展时间（TTP）6．8个月;FOLFOX6组RR为51．6％,TTP为7．1个月;两组比较各项指标差异无统计学意义（P〉0．05）。不良反应中XELOX组手足综合征发生率高于FOLFOX组,Ⅲ、Ⅳ度中性粒细胞减少发生率低于FOLFOX6组。结论：XELOX方案一线治疗晚期结、直肠癌有确切疗效,不良反应能耐受,与FOLFOX6方案相当,但XELOX方案用药更为方便,安全性更好。     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?     

Cancer immunotherapy

Unprecedented progress has seen made in the last decade in the field of cancer immunotherapy. The recent approval of nivolumab （Opdivo）, the first anti-programmed cell death-1 （PD-1） antibody, for metastatic melanoma in Japan, marked a milestone in the rapidly advancing field of cancer immunotherapy. Nivolumab together with ipilimumab （Yervoy）, the anti-cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） antibody, are the first 2 drugs in the class of ＂immune checkpoint inhibitors＂ that have delivered impressive responses in patients with metastatic melanoma and renal cell cancer （RCC） as well as a variety of solid tumors.     

Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 or elmex gelee. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In nonirradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 or elmex gelee led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected by remineralization than the dentine.     

Consultation multidisciplinaire pour les patients atteints d’une pathologie tumorale (carcinome infiltrant ou lésion précancéreuse) liée à HPV : la consultation multidisciplinaire papillomavirus

Given the recent increase in the number of human papillomavirus (HPV)-induced cancers in other locations than gynaecological, the number of patients with two cancers at distinct sites, and because of the lack of exhaustive data, we decided to create a multidisciplinary network around an HPV consultation at the Georges-Pompidou European Hospital (HEGP). This network aims to set up the best tools for detecting HPV-associated “multisite” precancerous lesions in order to determine the possible impact of dedicated care for this at-risk population. This monthly consultation was created at the HEGP in June 2014. It is currently organized around five consultations: gynaecological, ENT, urological, digestive and immunological. Every patient who has been diagnosed with HPV-related cancer and whose care is provided at the HEGP is offered this particular follow-up: systematically, once the initial lesion has been treated, the patient is convened annually for a day during which it benefits from the consultations mentioned above. A consultation with a psychologist is systematically proposed. Local samples are taken at each site: a cytological examination, the analysis of known predictive and prognostic virological markers are carried out. This study fits more broadly in a theme of clinical and fundamental research around cancers related to HPV.     

Differentiation state and invasiveness of human breast cancer cell lines

Summary Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and ₁ and ₄ integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in anin vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in thein vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best within vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47D_CO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis.