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1.
目的: 探讨抗PD-1单抗联合化疗及抗血管生成药物治疗晚期黑色素瘤的疗效和安全性。 方法: 收集2020年4月至2021年6月在北京大学肿瘤医院接受抗PD-1单抗联合化疗药物替莫唑胺±顺铂、白蛋白结合型紫杉醇及抗血管生成药物贝伐珠单抗治疗的14例(男6、女8例)不可切除的晚期黑色素瘤患者的临床资料。主要研究终点为无进展生存期(PFS),次要终点为客观有效率(ORR)、疾病控制率(DCR)、总生存期(OS)及安全性数据(CTCAE 5.0标准)。 结果: 14例晚期黑色素瘤患者均纳入生存分析,中位随访时间为5.50个月(95% CI: 0~13.12个月),中位PFS为7.43个月(95% CI: 3.07~11.79个月),中位OS为13.50个月(95% CI: 5.19~21.81个月),中位起效时间为1.5个月;ORR为28.6%(4例均为部分缓解),DCR为85.7%;不良反应多为1~2级。结论: 抗PD-1单抗联合化疗及抗血管生成药物治疗在晚期黑色素患者中显示出初步的有效性及良好的安全性,此可能为晚期黑色素瘤的联合治疗策略提供了新思路。  相似文献   

2.
目的 系统评价含贝伐珠单抗不同联合方案治疗晚期结直肠癌的疗效与安全性。方法 计算机检索PubMed、EMbase、Web of Science、Cochrane Library 数据库截至2017年7月31日有关贝伐珠单抗维持治疗晚期结直肠癌的随机对照试验。按纳入排除标准筛选文献、资料提取和评价质量,采用RevMan 5.3 软件进行Meta 分析。 结果 共纳入8项研究,2 644例晚期结直肠癌患者。Meta分析显示,贝伐珠单抗维持治疗组(包括单药和联合化疗)前者无疾病进展生存期(PFS)和总生存期(OS)均优于无治疗组(HR=0.65,95% CI:0.53~0.78,P<0.001;HR=0.83,95% CI:0.71~0.98,P=0.020),但前者3~4级感觉神经障碍及高血压发生率高于后者(P=0.001,0.008)。贝伐珠单抗维持治疗组与持续治疗组对比,两者的PFS和OS相当(HR=1.05,95% CI:0.56~1.71,P=0.830;HR=1.11,95% CI:0.92~1.35,P=0.270),而后者3~4级感觉神经障碍、疲乏和手足综合征明显高于前者(P<0.001,0.020,0.040)。与单药贝伐珠单抗组比较,贝伐珠单抗抗抗联合厄洛替尼组能改善PFS和OS(HR=0.81,95% CI:0.67~0.96,P=0.020;HR=0.81,95% CI:0.67~0.99,P=0.040),但贝伐珠单联合厄洛替尼组3~4级皮疹发生率明显高于单药贝伐珠单抗组(P<0.001)。结论 贝伐珠单抗单药、联合低毒化疗药物或厄洛替尼,均可改善晚期结直肠癌患者PFS和OS,患者可耐受,贝伐珠单抗维持治疗可作为晚期结直肠癌维持阶段的优选治疗方案。  相似文献   

3.
目的:回顾性分析贝伐珠单抗联合化疗治疗转移性结直肠癌的临床疗效。方法:收集2011-1/2015-8年XX医院收治的晚期结直肠癌患者422例,观察组81例,方案为贝伐珠单抗联合化疗,对照组341例,方案为单纯化疗,两组化疗方案均以奥沙利铂(OXA)及伊立替康(CPT-11)为基础的化疗药物比较两组的临床疗效、安全性及远期生存期。结果:观察组中客观缓解率(RR)、临床获益率(CBR)分别为27.2%、82.7%,中位PFS、中位OS分别为8.5个月、23.1个月,对照组中客观缓解率(RR)、临床获益率(CBR)分别为13.0%、57.2%,中位PFS、中位OS分别为4.9个月、16.2个月,差异均具有统计学意义( 均P<0.001),观察组中一线化疗方案联合贝伐珠单抗的总有效率为89.7%,中位PFS、中位OS分别为10.3个月、23.1个月,二线化疗方案联合贝伐珠单抗的总有效率为69.0%,中位PFS、中位OS分别为6.8个月、16.2个月,差异均具有统计学意义(均P<0.05),贝伐珠单抗联合不同化疗方案(XELOX、FOLFOX、FOLFIRI、XELIRI)的中位OS分别为20.0、19.9、17.4、16.8个月,差异具有统计学意义(P=0.016);对照组分别对应中位OS为13.5、13.8、13.4、12.5个月,差异具无统计学意义(P=0.960)。观察组中左半肠癌与右半肠癌的中位OS分别为20.8、15.0个月,差异具有统计学意义(P=0.002),对照组中左半肠癌与右半肠癌的中位OS分别为14.9、11.8个月,差异具有统计学意义(P<0.001)。贝伐珠单抗相关不良反应有高血压13例、蛋白尿8例、皮疹7例、出血5例,但大多为1-2级,患者总体耐受性好。结论:贝伐珠单抗联合化疗能提高显著晚期结直肠癌的近期疗效及远期生存,副反应较小;一线化疗方案中贝伐珠单抗联合XELOX方案的远期疗效优于其他方案,且无论何种化疗方案,左半肠癌患者的预后明显优于右半肠癌的患者。  相似文献   

4.
摘 要:探索帕博利珠单抗(Pembrolizumab)与紫杉醇比较在PD-L1阳性晚期胃/胃食管结合部腺癌临床疗效和安全性的两项全球多中心、随机对照、Ⅲ期研究(Keynote-061和062)均以失败告终,导致FDA撤销了Keytruda(可瑞达)在该适应证上的应用。两项研究样本量分别为592例和763例,主要终点均为总生存(overall survival,OS)。结果显示:帕博利珠单抗单药对比紫杉醇二线治疗 PD-L1联合阳性分数(combined positive score,CPS)≥1患者中两组中位总生存期分别为9.1个月和8.3个月,风险比(hazard ratio,HR)为0.82(95%CI:0.66~1.03,P=0.042 1),中位无进展生存期(progression-free survival,PFS)分别为1.5个月和4.1个月,风险比为1.27(95%CI:1.03~1.57);一线治疗的患者(CPS1)帕博利珠单抗OS非劣效于化疗,HR为0.91(99.2%CI:0.69~1.18),PFS风险比为1.66(95%CI:1.37~2.01);帕博利珠单抗联合化疗组相比化疗疗效改善没有明显优势,OS风险比为0.85(95%CI:0.70~1.03);PFS风险比为0.84(95%CI:0.70~1.02)。但在安全性方面,帕博利珠单抗相对于化疗均表现出较好的安全性。帕博利珠单抗单药在晚期胃/胃食管结合部腺癌的研究结果为阴性,其研究策略、方案设计、统计分析、后续布局等均值得进一步讨论和思考。  相似文献   

5.
目的 观察贝伐珠单抗联合FOLFOX或FOLFIRI方案用于转移性结直肠癌一线及二线治疗的临床疗效和毒副反应。方法 回顾性分析2005年11月至2012年8月接受贝伐珠单抗联合FOLFOX或FOLFIRI方案作为一线及二线治疗的57例转移性结直肠癌患者的临床资料。采用RECIST 1.1版评价疗效,用NCI-CTC 3.0版评价不良反应,用Kaplan-Meier法进行生存分析。结果 57例结直肠癌患者中,19例(33.3%)获PR,28例(49.2%)获SD,有效率(RR)为33.3%,疾病控制率(DCR)为82.5%。贝伐珠单抗联合化疗用于一线与二线治疗患者的RR或DCR差异均无统计学意义(P>0.05);贝伐珠单抗联合FOLFOX方案与FOLFIRI方案的RR或DCR差异均无统计学意义(P>0.05)。57例患者的无进展生存期(PFS)及总生存期(OS)分别为8.83个月及14.80个月。一线与二线治疗及贝伐珠单抗联合FOLFOX方案与FOLFIRI方案的中位PFS或OS差异均无统计学意义(P>0.05)。主要不良反应包括白细胞减少、血小板减少及恶心呕吐。贝伐珠单抗相关的不良反应主要包括高血压3例,蛋白尿1例,鼻衄2例,均为1~2级,药物可以控制。结论 贝伐珠单抗联合化疗治疗转移性结直肠癌能够提高治疗疗效,不良反应可以耐受。  相似文献   

6.
  目的  探讨贝伐珠单抗联合化疗对复治晚期非鳞非小细胞肺癌(non-squamous non-small cell lung cancer,NSNSCLC)患者的疗效和安全性,分析影响预后的因素。  方法  回顾性分析2013年2月至2017年6月北京胸科医院收治的41例复治晚期NSN? SCLC患者的病例资料。其中腺癌38例,其他病理类型3例。19例患者为二线治疗,22例患者为二线以上治疗。表皮生长因子受体(epidermal growth factor receptor,EGFR)突变阳性18例,突变阴性23例。评价贝伐珠单抗联合化疗的疗效和安全性,对可能影响预后的因素进行单因素和多因素分析。  结果  所有患者均接受化疗联合贝伐珠单抗的治疗,化疗的平均周期数为3.1个,贝伐珠单抗治疗的平均周期数为5.0个。41例患者均可评价疗效。全组患者客观缓解率(objective response rate,ORR)为12.2%,疾病控制率(disease control rate,DCR)为82.9%。二线治疗与二线以上治疗的患者疗效接近,ORR分别为10.5%、13.6%(P=0.572),DCR分别为89.5%和77.3%(P=0.271),差异无统计学意义。中位无进展生存期(progression-free survival,PFS)和中位总生存期(overall survival,OS)分别为4.6个月(95%CI:3.619~5.581)、11.9个月(95%CI:9.797~14.003)。单因素分析提示EGFR突变、贝伐珠单抗治疗周期数 > 4个及女性患者获得更长的生存(χ2=19.673,P < 0.001;χ2=6.820,P=0.009;χ2=6.374,P=0.012)。多因素分析显示,EGFR突变状态、贝伐珠单抗治疗周期数为影响患者预后的独立危险因素(HR=0.129,P=0.001;HR=0.336,P=0.012)。常见的不良反应有骨髓抑制、出血、高血压、蛋白尿等,多数为1~2级。  结论  贝伐珠单抗联合化疗对复治晚期NSNSCLC患者疗效确切,不良反应可耐受,EGFR突变阳性、贝伐珠单抗使用4个周期以上的患者预后较好。   相似文献   

7.
目的:观察贝伐珠单抗联合mFOLFOX6对比mFOLFOX6治疗晚期转移性结直肠癌的疗效及不良反应,并探索性地分析了左右半结肠癌的疗效差异性。方法:选取2017年1月至2018年8月在江门市中心医院肿瘤科确诊的72例晚期转移性结直肠癌患者,贝伐珠单抗+mFOLFOX6组33例,mFOLFOX6组39例,分析两组的治疗效果、中位PFS、不良反应,并分析不同治疗方案对左右半结肠癌疗效的影响。 结果:贝伐珠单抗+mFOLFOX6组ORR为45.5%,DCR为84.8%;mFOLFOX6组ORR为38.5%,DCR为79.5%。Kaplan-Meier分析显示mFOLFOX6组与贝伐珠单抗+mFOLFOX6组的中位PFS分别为6.2个月和7.7个月(P=0.06)。COX多因素分析结果显示贝伐珠单抗+mFOLFOX6组及mFOLFOX6组的PFS差异有统计学意义(P=0.024),治疗线数对PFS的影响未达统计学差异(P=0.059)。Kaplan-Meier分析显示贝伐珠单抗+mFOLFOX6组中右半结肠癌的PFS为6.9个月,左半结肠癌的PFS为8.1个月(P=0.538);mFOLFOX6组中右半结肠癌的PFS为6.37个月,左半结肠癌的PFS为6.2个月(P=0.209)。两组的不良反应主要为胃肠道反应、骨髓抑制及神经毒性。与贝伐珠单抗相关的不良反应主要为高血压、蛋白尿及血栓形成,除1例高血压为Ⅲ级外,其余均为Ⅰ-Ⅱ级。结论:贝伐珠单抗+mFOLFOX6治疗晚期转移性结直肠癌患者疗效好,不良反应可耐受,对左半结肠癌的PFS有获益的趋势。  相似文献   

8.
目的:重新评价卡瑞利珠单抗联合阿帕替尼治疗原发性肝癌(PHC)的有效性和安全性。方法:回顾性收集2019年1月至2021年5月在安徽医科大学附属第一医院确诊的PHC患者的临床资料。所有患者均接受卡瑞利珠单抗200 mg q3w联合阿帕替尼250 mg qd×21 d治疗。应用卡方检验进行基线特征比较,采用Kaplan-Meier法进行生存分析,从中估计中位总生存期(OS),然后采用Log-Rank检验进行比较;采用单因素Cox回归分析预测影响OS的因素。结果:本研究共纳入43例PHC患者,一线治疗患者的客观缓解率(ORR)为23.3%(7/30),二线及以上治疗患者的ORR为15.4%(2/13)。两组患者的疾病控制率(DCR)分别为83.3%(25/30)和61.5%(8/13),中位无进展生存期(PFS)分别为5.0个月(95%CI 3.2,6.8)和4.0个月(95%CI 1.7,6.3)(P=0.514),中位OS分别为13.0个月(95%CI 11.2,14.8)和9.0个月(95%CI 2.8,15.2)(P=0.179)。在43例患者中,33例(76.7%)存在3级或以上...  相似文献   

9.
目的探讨贝伐珠单抗在宫颈癌肺转移中的有效性及安全性。方法回顾性分析青岛市中心医院2015—2018年间收治的宫颈癌肺转移患者资料。Cox模型多因素分析影响宫颈癌肺转移患者预后因素。分层分析使用贝伐珠单抗组与未使用贝伐珠单抗组的预后差异。结果研究共纳入31例宫颈癌肺转移患者。7例(23%)仅发生了肺转移, 24例(77%)发生了多部位转移;复发后9例接受了局部治疗包括手术和放疗, 22例仅接受化疗;15例(48%)接受了贝伐珠单抗治疗, 16例(52%)未接受贝伐珠单抗治疗。平均无进展生存(PFS)时间20.5个月, 平均复发后生存(SAR)时间20.0个月, 平均总生存(OS)时间40.5个月。多因素分析显示初治分期(HR=6.247, 95%CI为1.294~30.156, P=0.023), 复发后未接受手术或放疗者(HR=5.903, 95%CI为1.211~28.780, P=0.028), 复发后未接受贝伐珠单抗治疗(HR=21.475, 95%CI为3.637~126.818, P=0.001)是影响生存时间的独立危险因素。分层分析显示复发后未手术或放疗者, 接受贝伐珠单抗...  相似文献   

10.
目的:评价贝伐珠单抗联合替莫唑胺剂量密度方案治疗复发胶质瘤的疗效及不良事件。方法:回顾性分析20例接受过贝伐珠单抗联合替莫唑胺剂量密度方案治疗的复发胶质瘤患者的临床资料并进行生存随访。依据RANO标准评价客观疗效,应用Kaplan-Meier 法进行生存分析,不良事件评价依据CTCAE 4.0版标准。结果:20例复发胶质瘤患者的临床获益率和客观反映率可达到85%和60%,中位PFS和中位OS分别为3个月(1.5~11个月)和6.5个月(3~15个月)。主要不良事件为高血压。结论:贝伐珠单抗联合替莫唑胺剂量密度方案治疗复发胶质瘤安全有效,且耐受性良好。  相似文献   

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New and emerging radiosensitizers and radioprotectors   总被引:3,自引:0,他引:3  
The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.  相似文献   

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The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.  相似文献   

15.
The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.  相似文献   

16.
目的:探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法:大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果:VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组(P〈0.05);在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义(P〈0.01)。结论:大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关(P〈0.05)。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。  相似文献   

17.
大量研究表明肿瘤细胞可表达β受体,而一些神经递质、药物和社会心理因素可能通过β受体影响肿瘤的生长和转移,β受体激动剂、β受体阻滞剂以及抑郁等社会心理因素可加强或削弱这种作用。这为表达β受体肿瘤的治疗开辟了新的道路,提供了新的治疗靶点。  相似文献   

18.
Epidemiologic evidence on the relation between occupational and environmental radiation and cancer is reviewed. Studies of pioneering radiation workers, underground miners, and radium dial painters revealed excess cancer deaths and contributed to the setting of radiation protection standards and to theories of carcinogenesis. Occupational exposures today are generally much lower than in the past, thus any associated increases in cancer will be difficult to detect. Pooling investigations of these more recently exposed workers, however, has the potential to validate current estimates of risk used in radiation protection. New information on the effects of chronic radiation exposure also may come from studies in the former Soviet Union of Chernobyl clean-up workers and of workers at the Mayak nuclear facilities. Studies of environmental radiation exposures, other than radon, are largely inconclusive, due mainly to the difficulties in detecting the low risks associated with low dose exposures. Thyroid cancer, however, has been linked to environmental radiation from the Chernobyl accident and from nuclear weapons tests. Low-level radiation released during normal operations at nuclear plants has not been found to increase cancer rates in surrounding populations. Radon, a human carcinogen, is the most ubiquitous exposure to human populations; remediating high residential-radon levels is recommended, recognizing that the exposure can never be removed completely because it occurs naturally.  相似文献   

19.
This review describes a new vision for future directions in the study of metastatic cancer biology and pathology. It is based upon clinical and experimental observations on the constituent cell lineages within a neoplasm and on tumour-host interactions. The vision incorporates information from studies in population biology, developmental biology and experimental pathology as well as investigations upon human malignant disease. The assembled information reveals that invasion and metastasis are supra-cellular manifestations of "emergent behavior" among combinations of normal and malignant cell lineages in vivo. Emergent behavior is a combinatorial interactive process in which a population displays new traits which cannot be achieved by individuals acting separately and which subside when the specific population mix disaggregates. Disruption of such pathological interactions in the field of a developing primary or secondary tumour is, therefore, required to disable the malignant population and arrest progression without tissue destruction. These conclusions originate, in part, from principles which govern the sociobiology and group behavior of bees, ants, fish, birds and human societies. In all these social organisms, external factors can disrupt signaling mechanisms and induce expanding self-perpetuating rogue behavior, leading to social disintegration. These principles also apply to cellular societies composing higher animals, which likewise need intrinsic rules to maintain social order and avoid anarchy, and recognition of this is essential for advancing future research on the mechanisms involved in carcinogenesis and metastasis. Summarised evidence is presented here to support the conclusion that miscommunications between cells and tissues in the region of the developing tumour and its metastases are the main direct perpetrators of malignant disease. Genetic lesions (mutations, deletions, translocations, reduplications, etc.), commonly seen in cancers, can significantly disrupt important molecular pathways in the networks of communications needed to sustain orderly tissue/organ structure and function. However, genetic lesions can also, themselves, be induced by abnormal cell interactions initiated by extrinsic carcinogenic agents such as chemicals, viruses, hormones and radiation. The evidence shows that, irrespective of the initiating cause, it is this miscommunication in the region of a developing tumour and its metastases that is ultimately responsible for the emergence and progression of the disease. The article describes how this information collectively, provides a framework for designing specific novel therapeutic approaches targeting the cell and tissue interactions driving tumour metastasis and its manifold effects on the whole body.  相似文献   

20.
Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60–3.53) and 1.64 (95% CI 1.02–2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63–1.13) for CM and 1.03 (95% CI 0.95–1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.  相似文献   

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