易瑞沙治疗晚期非小细胞肺癌的临床获益分析

目的：探讨选择性表皮生长因子受体抑制剂易瑞沙（IRESSA）治疗晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）的临床疗效及不良反应。方法：对既往化疗失败或不能耐受拒绝化疗的晚期NSCLC患者23例，单药IRESSA 250mg，口服，每日1次，服用至病情进展或出现不可耐受的不良反应。患者分别在治疗后30、90d对其疗效及不良反应进行观察统计。结果：23例中22例可评价疗效，其中CR1例，PR6例，SD10例，PD5例，有效率31．8％（7／22），患者疾病控制率（CR＋PR＋SD）77．3％（17／22）。治疗后30d肿瘤相关症状缓解率为73．9％（17／23）。Karnofsky评分，治疗前总分数900，人均39．1；治疗后总分数1380，人均60；治疗前后比较差异有统计学意义，t=3．18，P=0．004。常见不良反应为腹泻和皮肤改变，Ⅳ级占4．3％（1／23）。结论：IRESSA单药对化疗失败或不能耐受的晚期NSCLC疗效确切，改善症状明显，用药方便，不良反应轻。     

易瑞沙在晚期非小细胞肺癌化疗失败后的作用

目的探讨选择性表皮生长因子受体酪氨酸激酶抑制剂易瑞沙(IRESSA)单药治疗化疗失败的晚期非小细胞肺癌(NSCLC)的疗效及不良反应。方法既往化疗失败的Ⅳ期NSCLC患者52例,其中二线治疗失败者占77.0%。IRESSA250mg,口服,每日1次,服用至病情进展或出现不可耐受不良反应。患者分别在治疗后1个月、3个月及以后每2个月复查。结果本组52例均可评价疗效,其中PR11例,NC17例,PD24例,有效率21.2%,稳定率32.7%,疾病控制率(PR NC)为53.8%,无CR。中位肿瘤进展时间(TTP)为3.5个月。随诊>12个月的患者22例,1年生存率为31.8%,肿瘤相关症状缓解率为52.9%。常见不良反应为Ⅰ、Ⅱ度皮肤改变和腹泻,Ⅲ度不良反应占7.6%,其中1例因转氨酶升高结束治疗。结论IRESSA单药对化疗失败的晚期NSCLC疗效明确,并可用于一般状况评分较差的患者,不良反应较轻,是二、三线用药的良好选择。     

吉非替尼治疗晚期复治性非小细胞肺癌的临床研究

目的探讨应用吉非替尼(IRESSA)治疗晚期非小细胞肺癌(NSCLC)患者的疗效及其对生活质量的影响。方法既往化疗失败的Ⅲb-Ⅳ期NSCLC患者41例,其中二线化疗失败者占85.4%(35/41)。IRESSA 250 mg口服,每日1次,服药至病情进展或出现不能耐受的不良反应。患者分别在治疗后1个月、2个月和以后每3个月复查。结果本组41例患者均可评价疗效,其中PR 18例,SD 14例,PD 9例,有效率为43.9%(18/41),疾病控制率(PR SD)为78.0%(32/41)。男性患者和女性患者的有效率分别为42.1%和45.5%(P>0.05)。至随访结束,41例患者中,有22例(53.7%)存活,其中位生存时间(MST)为10.1个月;19例死亡患者的疾病进展时间(TTP)为2.7个月,MST为5.0个月;PR患者的MST为13.3个月。全组患者症状改善率为78.0%。服药28 d,KPS评分提高20±5分,无Ⅲ-Ⅳ度毒性反应。结论IRESSA单药对化疗失败的晚期NSCLC疗效确切,并可用于一般状况评分较差的患者,其不良反应轻,是二三线用药的良好选择。     

易瑞沙治疗化疗失败的晚期非小细胞肺癌

目的观察易瑞沙治疗化疗失败晚期非小细胞肺癌的疗效和不良反应。方法易瑞沙每天口服250mg治疗化疗失败的30例晚期非小细胞肺癌,1个月以后进行疗效评价,无进展者继续服用,之后每个月行CT检查评价疗效并临床密切观察,病情进展或不能耐受相关毒性者则停止使用易瑞沙。结果30例均可评价疗效,无CR者,PR6例(20.0%),SD14例(46.7%),PD10例(33.3%)。有效率(CR PR)为20.0%,疾病控制率(CR PR SD)66.7%,全组中位无进展生存期为3.0个月(0.7～29.0个月),中位生存期6.4个月(1.7～39.0个月)。主要不良反应包括皮疹22例,腹泻2例。没有患者因毒性不能耐受而停药。结论易瑞沙对化疗失败的晚期非小细胞肺癌具有一定疗效,不良反应轻微。     

易瑞沙治疗化疗失败非小细胞肺癌的临床观察

为评估易瑞沙(IRESSA)治疗化疗失败的非小细胞肺癌(NSCLC)的临床效果和毒副反应,2004年1月~2005年4月对31例曾经一线化疗治疗失败的NSCLC患者推荐给予易瑞沙250mg,口服,1次/d,结果总有效率(RR)41·9%(13/31),临床受益率(CBR)64·5%(20/31),常见毒副反应为食欲减退、轻度腹泻、皮疹和痤疮。1例患者死于重症间质性肺病变。初步的临床观察结果显示,易瑞沙对于一线化疗失败或化疗无效的晚期NSCLC肯定有效,能较好地缓解疾病相关症状,毒副反应轻微,大多可耐受。     

健择联合顺铂治疗老年晚期非小细胞肺癌患者的临床疗效观察

为了观察健择联合顺铂治疗老年(≥60岁)晚期(Ⅲ期及Ⅳ期)非小细胞肺癌(NSCLC)的疗效和毒副反应,探索适于老年人NSCLC的治疗方案。将48例患者分为治疗与观察两组,治疗组23例,d1、d8。健择1200mg/m2,静脉滴入,d1、d8;给予顺铂100mg/m2,静脉滴入,d1、d8。28d为1个周期。对照组25例采用单纯支持对症治疗。治疗组完全缓解(CR)4例,部分缓解(PR)7例,稳定(SD)8例,进展(PD)4例,有效率47·8%;对照组完全缓解(CR)0例,部分缓解(PR)2例,有效率8·0%,两组经统计学比较,差异有统计学意义,P<0·05。治疗组毒副反应有白细胞下降和血小板减少。初步研究的结果提示,健择联合顺铂治疗老年晚期NSCLC疗效较高,毒性可耐受。     

培美曲塞联合奈达铂治疗晚期乳腺癌的近期疗效

目的观察培美曲塞联合奈达铂治疗晚期乳腺癌的近期疗效及不良反应。方法 29例经蒽环类或紫杉类等药物化疗失败的晚期乳腺癌患者,给予培美曲塞联合奈达铂治疗,具体方案为:培美曲塞500 mg/m2静滴,第1天;奈达铂75 mg/m2静滴,第2天;3周1疗程,至少化疗2个疗程后评价疗效及不良反应。结果 29例患者均可评价疗效及不良反应。2例完全缓解(CR),10例部分缓解(PR),8例疾病稳定(SD),9例疾病进展(PD),总有效(CR+PR)12例(41.4%);疾病控制(CR+PR+SD)20例(69.0%)。主要不良反应为骨髓抑制、皮疹和胃肠道反应,经对症处理后均缓解。结论培美曲塞联合奈达铂治疗晚期乳腺癌疗效可靠,毒性反应轻,可耐受。     

脂质体紫杉醇联合卡铂治疗老年晚期头颈部肿瘤的临床观察

目的探讨脂质体紫杉醇联合卡铂治疗老年晚期头颈部肿瘤的近期疗效及安全性。方法对22例老年晚期头颈部肿瘤进行化疗,方案为脂质体紫杉醇135 mg/m2,d1;卡铂300 mg/m2,d2,21~28天重复。2个周期后评价疗效及不良反应。结果 22例中21例可评价疗效,共完成周期数72个,完全缓解(CR)2例,部分缓解(PR)6例,稳定(SD)9例,进展(PD)4例,总有效率(CR+PR)38.1%,疾病控制率(CR+PR+SD)80.9%,主要不良反应为骨髓抑制、胃肠道反应、脱发、疲乏,其中Ⅲ~Ⅳ级不良反应为8例(38.1%),无化疗相关性死亡。结论脂质体紫杉醇联合卡铂治疗老年晚期头颈部肿瘤有较好的近期疗效,反应可耐受。     

吉非替尼治疗化疗失败后的晚期非小细胞肺癌30例临床观察

目的:观察吉非替尼治疗含铂化疗后失败的晚期非小细胞肺癌(NSCLC)患者的疗效及毒副反应.方法:对30例晚期非小细胞肺癌患者给予吉非替尼250 mg/d口服治疗,持续用药直到疾病进展或出现不可耐受的毒副反应.结果:30例患者均可评价疗效及毒副反应,服药2个月后行病灶CT检查,CR 2例(6.7%),PR 6例(20.0%),SD 14例(46.6%),PD 8例(26.7%),总有效率(CR+PR)26.7%,疾病控制率(CR+PR+SD)73.3%.复发患者中位肿瘤进展时间为7个月,全组患者中位总生存时间(OS)为18个月,1年生存率为 84.6%,2年生存率为22.0%.不良反应主要为Ⅰ～Ⅱ度皮疹和腹泻,一般无需特殊处理,可以自行缓解.结论:吉非替尼是治疗晚期非小细胞肺癌的有效靶向治疗药物,可用于含铂药物失败后的二线或三线治疗.药物相关的毒副反应主要为轻度的皮疹及腹泻,患者容易耐受.     

吉西他滨联合顺铂治疗TP方案失败的老年人非小细胞肺癌22例

目的 探讨紫杉醇+顺铂(TP)方案失败后使用吉西他滨(商品名:泽菲)+顺铂(GP)方案治疗65岁以上非小细胞肺癌(NSCLC)患者的疗效及不良反应.方法 22例使用TP方案治疗失败的NSCLC患者改用GP方案,即吉西他滨1000 mg/m2,第1、8天;顺铂60～80 mg/m2,第1天至第3天.完成2个周期后进行临床疗效和不良反应评价.结果 22例中总有效率40.9%,其中CR 1例,PR8例,SD 7例,PD 6例.骨髓抑制和腹泻为主要不良反应,但可以耐受,经治疗后可恢复.结论 吉西他滨联合顺铂治疗TP方案失败的老年NSCLC具有较好的耐受性和一定的临床疗效,不良反应轻,经处理可以恢复.     

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.