盐酸埃克替尼治疗EGFR突变晚期肺腺癌的预后因素分析

目的 探讨晚期肺腺癌表皮生长因子受体（EGFR）突变患者应用表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）盐酸埃克替尼片治疗与预后的关系。方法 入组河北省胸科医院基因检测提示EGFR19、21基因突变且接受盐酸埃克替尼片治疗的晚期肺腺癌患者,分析其临床特征、EGFR基因突变亚型及不同位点与预后的关系。结果 全组共纳入101例晚期肺腺癌患者,EGFR基因19外显子缺失突变（EGFR Del19）58例,21外显子点突变（EGFR L858R）43例。全组患者客观缓解率达63.4%,中位无疾病进展时间（mPFS）和中位生存时间（mOS）分别为13个月和27个月。EGFR Del19对比EGFRL858R及EGFR19突变746~750位点对比其他突变位点的患者mPFS和mOS均增高。多因素分析显示,转移部位数和有无胸膜转移为OS的独立影响因素（P=0.027, P=0.041）,转移部位数≤3和无胸膜转移组患者的mOS分别为29个月和27个月。结论 盐酸埃克替尼片治疗晚期肺腺癌患者EGFR不同突变亚型和位点总生存差异不显著,转移部位数≤3和无胸膜转移的患者总生存期更长。     

盐酸埃克替尼一线治疗晚期肺腺癌的临床疗效观察

背景与目的分子靶向治疗药物盐酸埃克替尼治疗复治晚期非小细胞肺癌具有较好的疗效和安全性。本文观察盐酸埃克替尼一线治疗晚期肺腺癌的近期疗效和毒副反应。方法对2011年8月-2012年11月间收治的56例初治晚期肺腺癌患者,口服盐酸埃克替尼125 mg,每日3次,评价近期疗效和不良反应。结果 56例肺腺癌患者的客观有效率为46.4%(26/56),疾病控制率为78.6%(44/56)。20例患者进行了EGFR基因突变检测,18例患者EGFR基因突变阳性,EGFR突变阳性患者的客观有效率为66.7%(12/18),疾病控制率为94.4%(17/18)。不吸烟、EGFR基因突变阳性和出现皮疹的患者客观有效率高于吸烟、EGFR基因野生型和突变情况未知、未出现皮疹的患者(P<0.05)。治疗相关毒副反应主要为轻度皮疹(28.5%)和腹泻(12%)。结论盐酸埃克替尼一线治疗晚期肺腺癌疗效肯定,不良反应轻微,对于EGFR突变阳性患者有效率更高。     

第三代TKIs在EGFR突变非小细胞肺癌中的应用

肿瘤治疗的个体化带来了临床实践变革。近年来,表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）对EGFR阳性突变的非小细胞肺癌显示出良好的抗肿瘤活性。第三代EGFR-TKIs相对于一代EGFR-TKI,显著提高了EGFR突变晚期非小细胞肺癌治疗的有效率、无进展生存期及总生存期,且对脑转移病灶有良好的疗效,对可手术的EGFR突变非小细胞肺癌术后辅助治疗也体现了无病生存获益,在联合放疗应用于局部晚期及晚期寡转移EGFR突变非小细胞肺癌中优势明显。     

奥希替尼治疗不同表皮生长因子受体基因突变型晚期肺腺癌疗效分析

目的 分析一代表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)耐药后奥希替尼治疗不同EGFR基因突变的晚期肺腺癌临床疗效.方法 回顾性分析2015年1月至2019年10月郑州大学第一附属医院收治的82例EGFR敏感突变且第1代EGFR-TKIs耐药后基因检测T790M突变的晚期肺腺癌患者的临床资料.将50例19外...     

晚期肺腺癌EMT和EGFR突变状态的关系及其对吉非替尼治疗疗效的影响

目的：探讨晚期肺腺癌上皮间质转化（EMT）与表皮生长因子（EGFR）突变的关系及其对吉非替尼治疗敏感性的关系。方法通过检测78例晚期肺腺癌EGFR突变情况和E-cadherin/β-catenin表达情况,对EGFR突变的晚期肺腺癌患者一线使用吉非替尼,EGFR未突变的晚期肺腺癌一线化疗失败后二线使用吉非替尼治疗,观察吉非替尼治疗的疗效和无进展生存时间（PFS）。结果晚期肺腺癌EGFR突变患者E-cadherin表达高于EGFR未突变患者。EGFR突变且E-cadherin/β-catenin阳性表达者疾病控制率（DCR）略高于异常表达者,虽差异无统计学意义,但EGFR突变同时E-cadherin/β-catenin阳性表达者显示了更长的PFS。EGFR未突变的晚期肺腺癌二线吉非替尼治疗患者临床获益率低。结论晚期肺腺癌患者EGFR突变者常伴随E-cadherin高表达,同时存在EG-FR突变和E-cadherin/β-catenin高表达者显示更长的PFS;不建议EGFR未突变的晚期肺腺癌病例二线使用吉非替尼。     

埃罗替尼治疗吉非替尼耐药的晚期非小细胞肺癌有效1例

晚期非小细胞肺癌(NSCLC)预后差,以化疗为主的联合治疗只能降低死亡风险26%-32%[1].近年来,非小细胞肺癌的靶向治疗成为研究热点,其中尤以表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)进展最快,其代表药物吉非替尼(gefitinib、iressa)和埃罗替尼(erlotinib、tarceva).我科用埃罗替尼治疗吉非替尼耐药的晚期非小细胞肺癌(NSCLC)一例取得了较好疗效,现报告如下.     

盐酸埃克替尼治疗晚期非小细胞肺癌的临床观察

目的:观察盐酸埃克替尼治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）的疗效、安全性及其影响因素。方法:回顾性分析云南省肿瘤医院2013年11月-2016年2月收治的接受盐酸埃克替尼治疗的晚期NSCLC患者56例,对患者疗效、生存期及毒副反应进行评价。结果:56例患者均可评价疗效,客观有效率（objective response rate,ORR）为30.4%,疾病控制率（disease control rate,DCR）为83.9%,中位无进展生存期（progression free survival,PFS）为9个月。腺癌患者的DCR、PFS均优于鳞癌患者（P＜0.05）。12例患者进行EGFR基因检测,均为突变阳性,EGFR突变患者的ORR为58.3%,DCR为100%,PFS为9个月。EGFR突变患者的ORR优于EGFR状态未知患者（P＜0.05）。毒副反应主要为轻度的皮肤毒性和腹泻。结论:盐酸埃克替尼是治疗晚期NSCLC的有效药物,毒副反应较轻,腺癌患者能获得较好的疗效,EGFR突变患者的疗效更好。     

吉非替尼治疗69例老年肺腺癌的临床分析

背景和目的探讨上皮生长因子受体(EGFR)酪氨酸激酶抑制剂(EGFR-TKI)吉非替尼(Gefitinib,Iressa,易瑞沙)治疗老年晚期肺腺癌的疗效及安全性。方法对2002年10月至2006年12月在中国医学科学院肿瘤医院治疗的69例65岁以上患者的临床特点、治疗效果及生存时间进行了回顾性分析。所有患者均口服吉非替尼250 mg/天,直到病变进展或不能耐受。结果吉非替尼总有效率24.6%,疾病控制率88.4%,中位生存时间15个月,1年生存率62.2%。年龄<75岁,不吸烟,一线治疗患者的有效率明显高于≥75岁,吸烟,二线以上治疗的患者。女性,肺泡细胞癌和不吸烟患者的生存时间优于男性,腺癌和吸烟患者。吉非替尼的不良反应较轻,主要表现为轻度皮疹和腹泻。结论吉非替尼治疗老年晚期肺腺癌安全有效。     

非小细胞肺癌患者EGFR基因突变与吉非替尼临床疗效关联

目的:评估吉非替尼（Gefitinib）疗效和晚期难治性非小细胞肺癌（NSCLC）患者表皮生长因子受体（EGFR）突变情况的关联。方法:121名晚期难治性非小细胞肺癌患者,均是经过一线化疗方案失败的中晚期非小细胞肺癌患者,每日予以口服吉非替尼250mg治疗,直到疾病进展或出现不可耐受的毒副反应为止。在开始治疗之前检测EGFR18、19、21位点,于治疗期间进行常规检查和规范的随访。分析疗效、突变以及中位生存期之间的关联。结果:在115名有效随访的患者中,13例完全缓解,25例部分缓解,38例稳定,39例病情进展。疾病控制率66.3%。1年和2年生存率分别为59.7%和26.9%。中位生存期16个月。115人中有38例病人存在EGFR突变。EGFR突变的病人表现出对吉非替尼较敏感。不吸烟的女性患者有较好的疗效和较长的生存期。而患者年龄、一线化疗周期、肿瘤分期的组间差异对于生存期的影响都无显著差异。结论:吉非替尼在女性不吸烟非小细胞肺癌患者中疗效是确定的。西部女性肺腺癌患者拥有较高的突变率和较长的生存时间。     

埃克替尼在晚期非小细胞肺癌EGFR状态明确的患者中的疗效分析

背景与目的 埃克替尼是国内第一个口服的表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶受体抑制剂,在体内外实验研究中显示出对非小细胞肺癌的明显抑制作用.Ⅲ期临床研究ICOGEN显示埃克替尼对复治晚期非小细胞肺癌疗效不劣于吉非替尼.本研究探讨在晚期非小细胞肺癌明确EGFR状态的患者中(EGFR野生型和突变型)埃克替尼的疗效和安全性.方法 回顾性分析2011年8月-2012年8月在浙江省肿瘤医院就诊并行埃克替尼治疗的晚期非小细胞肺癌患者,Kaplan-Meier法进行生存分析和比较.结果 49例患者明确了EGFR突变状态并行埃克替尼治疗,49例患者中13例为野生型,36例为突变型.突变患者的客观缓解率和疾病控制率分别为58.3％和88.9％,野生型患者的客观缓解率和疾病控制率分别为7.7％和53.8％.突变和野生型患者的中位无进展生存期为9.5个月和2.2个月(P＜0.001).36例突变患者中一线治疗19例,二线及二线以上患者17例.一线和复治患者的中位无进展生存期(progression-free survival,PFS)分别为9.5个月和8.5个月(P=0.41).突变型患者的中位总生存期(overall survival,OS)尚未达到,野生型患者的OS为12.6个月.患者的不良反应以皮疹和腹泻为主,但多为轻到中度.结论 埃克替尼在EGFR突变患者中的疗效较好,可以作为EGFR突变患者的优选方案.患者的毒副反应多数可以耐受.     

Experience with Impedance Phlebography Compared with Venography

Venography is a particularly reliable method for the diagnosis of deep venous thrombosis but is not suitable as a screening test. Impedance phlebography represents another attempt to discover a simple, non-invasive and reliable method of detecting deep venous thrombosis. It does not, however, meet these criteria.     

Compliance with guidelines and correlation with outcome in patients with advanced germ-cell tumours

PurposeTo evaluate prior compliance with guidelines in patients treated with salvage chemotherapy for advanced germ-cell tumours (GCT).Patients and methodsData concerning the initial management of patients requiring salvage chemotherapy for GCT at Institut Gustave Roussy between 2000 and 2010 were obtained and correlated with recommendations for treatment. Criteria of non-compliance were defined based on guidelines. Compliance with guidelines, predictive factors for non-compliance and the impact on outcome were analysed.ResultsAmong 82 patients treated in the salvage setting, guidelines to initial treatment were followed in only 41 cases (50%). The most common non-compliance criteria were non-adherence to the planned dose (16%), an inappropriate interval between first-line chemotherapy cycles (16%), the lack of post-chemotherapy surgery (16%) and a long interval to post-chemotherapy surgery (48%). Compliance with standard care was better in cancer centres than in other hospitals (private or public) (Odd Ratio (OR): 6.9, P = 0.001). A poor-risk status according to the International Germ Cell Cancer Collaborative Group (IGCCCG) was also predictive of compliance in univariate but not in multivariate analysis. No significant difference in outcome after salvage chemotherapy was observed. Patients relapsing after non-compliant first-line therapy tended to be more easily salvaged, which is consistent with the fact that their initial treatment was inadequate. Some of these relapses were therefore probably not due to true biologically refractory disease.ConclusionGuidelines for first-line treatment are adhered to in only half the patients requiring salvage chemotherapy. As the only predictive factor for non-compliance was the treating centre, centralisation of patients with GCT in well-trained hospitals should be recommended.     

Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer

BackgroundMethylnaltrexone (MNTX), a peripherally acting μ-opioid receptor (MOR) antagonist, is FDA-approved for treatment of opioid-induced constipation (OIC). Preclinical data suggest that MOR activation can play a role in cancer progression and can be a target for anticancer therapy.Patients and methodsPooled data from advanced end-stage cancer patients with OIC, despite laxatives, treated in two randomized (phase III and IV), placebo-controlled trials with MNTX were analyzed for overall survival (OS) in an unplanned post hoc analysis. MNTX or placebo was given subcutaneously during the double-blinded phase, which was followed by the open-label phase, allowing MNTX treatment irrespective of initial randomization.ResultsIn two randomized, controlled trials, 229 cancer patients were randomized to MNTX (117, 51%) or placebo (112, 49%). Distribution of patients' characteristics and major tumor types did not significantly differ between arms. Treatment with MNTX compared with placebo [76 days, 95% confidence interval (CI) 43–109 versus 56 days, 95% CI 43–69; P = 0.033] and response (laxation) to treatment compared with no response (118 days, 95% CI 59–177 versus 55 days, 95% CI 40–70; P < 0.001) had a longer median OS, despite 56 (50%) of 112 patients ultimately crossing over from placebo to MNTX. Multivariable analysis demonstrated that response to therapy [hazard ratio (HR) 0.47, 95% CI 0.29–0.76; P = 0.002) and albumin ≥3.5 (HR 0.46, 95% CI 0.30–0.69; P < 0.001) were independent prognostic factors for increased OS. Of interest, there was no difference in OS between MNTX and placebo in 134 patients with advanced illness other than cancer treated in these randomized studies (P = 0.88).ConclusionThis unplanned post hoc analysis of two randomized trials demonstrates that treatment with MNTX and, even more so, response to MNTX are associated with increased OS, which supports the preclinical hypothesis that MOR can play a role in cancer progression. Targeting MOR with MNTX warrants further investigation in cancer therapy.Clinical trials numberNCT00401362, NCT00672477.     

Costs associated with complications are lower with capecitabine than with 5‐fluorouracil in patients with colorectal cancer

BACKGROUND:

Capecitabine, an oral alternative to 5‐fluorouracil (5‐FU) in patients with colorectal cancer (CRC), has equal clinical efficacy and a favorable safety profile; however, its use may be limited because of unit cost concerns. In this study, the authors measured the cost of chemotherapy‐related complications during treatment with capecitabine‐ and 5‐FU–based regimens.

METHODS:

Patients with CRC who received at least 1 administration of capecitabine or 5‐FU during 2004 and 2005 were identified from the Thomson MarketScan research databases. Monthly frequency and cost for 23 complications were recorded. Logistic regression was used to predict complication probability. General linear models were used to predict monthly complication cost and total monthly expenditure.

RESULTS:

In total, 4973 patients with CRC met the inclusion criteria for this analysis. Although the most frequently observed complications were the same between capecitabine and 5‐FU (nausea and vomiting, infection, anemia, neutropenia, diarrhea), each was observed with greater frequency in 5‐FU–based regimens. The mean predicted monthly complication cost was significantly higher (by 136%) with 5‐FU monotherapy than with capecitabine monotherapy (difference, $601; 95% confidence interval [95% CI], $469‐$737). In addition, the mean predicted monthly complication cost for 5‐FU+oxaliplatin was higher than the cost with capecitabine plus oxaliplatin (difference, $1165; 95% CI, $892‐$1595). When acquisition, administration, and complication costs were taken into consideration, there were no significant differences in the total cost between capecitabine regimens and 5‐FU regimens.

CONCLUSIONS:

Capecitabine compared well with 5‐FU–based therapy in patients with CRC and was associated with lower complication rates and associated costs. Cancer 2009. © 2009 American Cancer Society.     

Living with secondary breast cancer: coping with an uncertain future with unmet needs

JOHNSTON S.R.D. (2010) European Journal of Cancer Care 19 , 561–563 Living with secondary breast cancer: coping with an uncertain future with unmet needs     

奥沙利铂联合羟基喜树碱治疗晚期胃癌临床分析

背景与目的体外及体内的临床研究显示,奥沙利铂(L-OHP)对多种肿瘤有显著抑制作用并与绝大多数抗癌药物具有相加或协同细胞毒作用.本文旨在观察L-OHP联合羟基喜树碱(HCPT)治疗晚期胃癌的近期疗效和患者耐受性,并与传统的化疗方案进行对比.方法采用非随机的分组方法将43例晚期胃癌患者分为L-OHP+HCPT方案组(治疗组)与Vp-16+CF+5-FU(ELF)方案组(对照组),其中男性28例,女性15例,中位年龄59岁,KPS评分≥60,观察两组的近期疗效和患者耐受性.结果治疗组24例有效率58.3%(14/24),对照组19例有效率42.1%(8/19).治疗组有效率高于对照组,两组差异有显著性(P<0.05).两组不良反应主要是骨髓抑制、恶心、呕吐、口腔炎、周围神经炎、静脉炎、脱发等,均在Ⅰ、Ⅱ度范围内.结论L-OHP联合HCPT方案治疗晚期胃癌疗效较好,不良反应可以耐受.     

Varicella-Zoster Virus Prophylaxis with Low-Dose Acyclovir in Patients with Multiple Myeloma Treated with Bortezomib

BackgroundVaricella-zoster virus (VZV) reactivation is a common complication in patients with multiple myeloma (MM) treated with bortezomib, with an incidence rate of 10%-60%. The aim of our study was to analyze the effect of acyclovir prophylaxis in this patient population.Patients and MethodsWe studied 98 consecutive patients with relapsed MM treated with bortezomib. Bortezomib 1.3 mg/m² was given on days 1, 4, 8, and 11 of a 21-day cycle. At first, patients did not receive any VZV prophylaxis, but because of the high incidence of VZV reactivation, VZV prophylaxis with acyclovir was implemented subsequently.ResultsA total of 11 patients treated with bortezomib did not have any VZV prophylaxis, and 4 of these 11 patients (36%) developed VZV reactivation in the form of herpes zoster. No VZV reactivations were observed in the 32 patients who received acyclovir 400 mg 3 times daily or the 55 patients who received acyclovir in a dose reduced to 400 mg once daily during bortezomib treatment.ConclusionVaricellazoster virus reactivation is a common and serious adverse effect of bortezomib treatment. Acyclovir 400 mg once daily is sufficient to protect from VZV reactivation in patients with MM treated with bortezomib.