Predictive factors associated with prolonged survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with gefitinib

This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. A total of 221 Japanese patients who received gefitinib (250 mg day(-1)) were examined retrospectively and potential predictive factors analysed. Overall response rate (ORR) was 24.4% and median survival time (MST) was 8.0 months. In a log-rank test, survival was significantly better in females, patients with adenocarcinoma, never-smokers, favourable performance status (PS) and patients with epidermal growth factor receptor (EGFR) mutation. The lower the smoking exposure (Brinkman Index (BI)=cigarettes per day x years smoked), the better the MST (BI 0: 14.5 months, BI <500: 9.5 months, BI 500 to <1000: 6.9 months, BI > or =1000: 4.0 months). Positive-EGFR mutation status and PS 0-1 were independent predictors of favourable prognosis by multivariate analysis. Prognosis was significantly different according to EGFR mutation status (with the same smoking status), but not according to smoking status (with the same EGFR mutation status). EGFR mutation status is the most important independent predictor of survival benefit with gefitinib treatment. Although differences in prognosis were observed according to relative smoking status and smoking exposure, the results suggested that smoking is not a direct predictor of prognosis, yet is a surrogate marker of EGFR mutation status.     

非小细胞肺癌患者体表面积与吉非替尼疗效的关系

目的探讨表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)患者体表面积(BSA)与口服吉非替尼疗效之间的关系。方法选取2010年1月至2016年9月间河南省内乡县人民医院收治的115例采用吉非替尼单药治疗的EGFR突变的NSCLC患者,使用Cox吉非替尼疗效与体表面积的关系。结果相比于BSA较高(≥1.5m~2)者,吉非替尼对BSA较低(<1.5m~2)患者的疗效更好。两者的总存活时间(OS)无显著差别,较低和较高BSA患者的无进展生存时间(PFS)分别是8.5个月和4.2个月,差异有统计学意义(P<0.05)。BSA对PFS具有显著影响,差异有统计学意义(P<0.05)。结论使用吉非替尼单药治疗的EGFR突变NSCLC患者的BSA越高PFS越低。     

Prognostic significance of AMPK activation in advanced stage colorectal cancer treated with chemotherapy plus bevacizumab

Background:

AMP-activated protein kinase (AMPK) has a central role in cellular energy sensing and is activated in preclinical tumour models following anti-vascular endothelial growth factor (VEGF) therapy. The possible predictive or prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs has not been investigated so far.

Methods:

Expression of components of the AMPK pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK pathway scores and clinico-pathological characteristics were assessed. Overall survival (OS) was estimated through Kaplan–Meier method, whereas hazard ratios were computed to identify prognostic factors.

Results:

Fourteen patients (29.2%) were included in the pAMPK-negative group (score ⩽5), whereas 34 patients (70.8%) were included in the pAMPK-positive group (score >5). The Spearman''s coefficient for the correlation between pAMPK and pACC scores in primary tumour samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P-value 0.0002) but not with PFS, whereas low pACC levels were associated both with worse OS and PFS (P-value 0.0007 and 0.01, respectively).

Conclusions:

Our findings suggest that high tissue AMPK activation is a prognostic biomarker in this cohort of metastatic colorectal cancer patients.     

Comparison of gefitinib and erlotinib in advanced NSCLC and the effect of EGFR mutations

Introduction

Erlotinib and gefitinib are tyrosine kinase (TK) inhibitors of epidermal growth factor receptor (EGFR) that are effective in treating non-small cell lung cancer (NSCLC). This study aimed to compare their clinical uses and the influence of EGFR mutation.

Methods

The usages of erlotinib and gefitinib in advanced NSCLC were analyzed. Clinical data and EGFR mutational status of tumors were collected.

Results

Seven hundred and sixteen (716) patients received gefitinib (n = 440) or erlotinib (n = 276) for stage IIIb or IV NSCLC. Erlotinib was prescribed more frequently than gefitinib in males (58.2% vs. 41.8%, p < 0.001), smokers (60.5% vs. 39.5%, p < 0.001), and non-adenocarcinoma (70.6% vs. 29.4%, p < 0.001). Of the 716 study patients, 327 underwent testing for EGFR mutations (170 with mutant EGFR and 157 with wild-type EGFR). Adenocarcinoma in patients with mutant EGFR and non-smoker status in patients with wild-type EGFR were associated with better overall survival after TK inhibitor treatment. In both patient groups with mutant EGFR or wild-type EGFR, the effectiveness of gefitinib and erlotinib, including drug response or overall survival, were not different.

Conclusions

Our study revealed the obvious disparity in drug selection between erlotinib and gefitinib in clinical practice. Type of TK inhibitors did not influence treatment outcomes in patients with EGFR mutation or wild-type EGFR.     

吉非替尼对于化疗失败的晚期肺腺癌的疗效及生存观察

目的：观察吉非替尼在化疗失败的晚期肺腺癌中的疗效、生存时间及影响因素。方法：收集２１例初始化疗失败的转移性肺腺癌,应用吉非替尼２５０ｍｇ口服,每日１次,直至出现有客观证据的病情进展,或出现不可耐受的不良反应。用Ｋａｐｌａｎ-Ｍｅｉｅｒ法拟定生存曲线,采用Ｌｏｇｒａｎｋ检验分析生存因素。结果：２１例患者中ＣＲ３例（１４.３％）,ＰＲ例８（３８.１％）,ＳＤ３例（１４.３％）,ＰＤ７例（３３.３％）。客观缓解率为５２.４％,疾病控制率为６６.７％。中位无进展生存时间（ＰＦＳ）为６个月,中位生存时间（ＯＳ）为８个月。１年生存率为３３.３％（７／２１）,２年生存率为９５％（２／２１）。好的ＰＳ评分与生存期延长显著相关（Ｐ＜０.０１）。结论：吉非替尼对既往化疗失败的晚期肺腺癌疗效好,能有效改善生存时间,体力状态评分与吉非替尼治疗的生存时间相关。     

Efficacy and tolerability of gefitinib in pretreated elderly patients with advanced non-small-cell lung cancer (NSCLC)

The activity and toxicity profile of gefitinib in non-small cell lung cancer (NSCLC) patients aged 70 years or older has been only partially evaluated. The aim of this study was to evaluate the response rate and safety of gefitinib in elderly NSCLC patients. Elderly NSCLC patients pretreated with chemotherapy and with at least one measurable lesion received gefitinib at the daily dose of 250 mg until disease progression, unacceptable toxicity or refusal. From August 2001 to May 2003, 40 consecutive elderly patients have been enrolled onto the study in three Italian institutions. We observed one complete (2.5%) and one partial response (2.5%), 18 disease stabilisations (NC: 45%) lasting at least 2 months, including six patients (15%) who had disease stabilisation of 6 months or longer, for an overall disease control rate of 50% (95% CI: 34.5-65.5%). The median duration of response was 4.4 months (range 1.7-9.2). The side effects were generally mild and consisted of diarrhoea and skin toxicity. Grade 1-2 diarrhoea occurred in 23.6%, and one patient experienced grade 4 diarrhoea, requiring hospitalisation. Grade 1-2 skin toxicity, including rash, pruritus, dry skin, and acne, occurred in 20 patients (52.6%). Gefitinib is safe and well tolerated in elderly pretreated NSCLC patients. The disease-control rate achieved suggests that this drug could represent a valid option in the management of this unfavourable subgroup of patients.     

重组人血管内皮抑素联合NP方案治疗晚期非小细胞肺癌的临床观察

目的:观察YH-16联合长春瑞滨和顺铂(NP)治疗晚期非小细胞肺癌(NSCLC)的近期疗效和安全性,同时探讨循环血管内皮细胞(CECs)与该方案疗效的相关性.方法:应用YH-16联合NP方案治疗晚期NSCLC 11例,观察其近期疗效及毒副反应.流式细胞法检测治疗前后外周血CECs数量.结果:在可评价疗效的11例患者中,CR 0例,PR 1例,SD 6例,PD 4例.初治患者3例,PR 1例,SD 2例.复治患者9例,其中二线治疗3例,均为SD;三线治疗3例,SD 1例,PD 2例;四线治疗2例,均为PD.该方案用药期间,除Ⅰ～Ⅱ度恶心呕吐及骨髓抑制,3例出现轻度心慌,4例出现轻度乏力,不影响继续用药.7例临床受益患者CECs由(0.67±0.20)%下降为(0.43±0.20)%,4例临床进展患者CECs由(0.69±0.25)%上升为(1.08±0.63)%.结论:YH-16联合 NP方案一线治疗NSCLC疗效满意,有可能使含铂一线甚至多线化疗失败者(身体状况良好者)继续临床受益;该方案安全性较好;CECs可能是一个较好的预测化疗联合抗血管生成治疗疗效的标志.     

99mTc-HL91 SPECT乏氧显像与非小细胞肺癌预后的关系

目的利用99mTc-HL91 SPECT乏氧显像,研究非小细胞肺癌(NSCLC)放疗中乏氧程度及乏氧变化与预后的关系。方法32例NSCLC患者,三维适形放射治疗前1～2 d行99mTc-HL91 SPECT检查,其中18例分别于放疗过程中接受30～40 Gy照射,放疗后1～2 d行99mTc-HL91 SPECT检查。利用感兴趣区(ROI)技术,计算靶与非靶的比值。治疗结束后,所有患者进行随访,分析放疗前及放疗中T与N比值的变化与放疗疗效及生存率的相关性。结果放疗中,T与N的比值逐渐下降(P=0.000)。放疗前,T与N比值较低组的有效率(P=0.002)和生存率均高于T与N比值较高组(P=0.043)。放疗前后,T与N比值变化较大组的放疗有效率与生存率高于变化较小组,差异无统计学意义。结论HL91 SPECT显像对NSCLC患者的预后有一定的预测价值。     

吉非替尼治疗晚期非小细胞肺癌49例疗效分析

肺癌是临床上最常见的恶性肿瘤,约占所有恶性肿瘤死亡的25%～30%。大多数患者在明确诊断时已为局部晚期或远处转移,失去根治性手术的机会。吉非替尼是表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor- tyrosine kinase inhibitor,EGFR-TKI),既能抑制肿瘤的增殖、侵犯,又能抑制肿瘤新生血管生成,同时还能诱导肿瘤细胞     

Prognostic significance of circulating tumor cells in advanced non-small cell lung cancer patients treated with docetaxel and gemcitabine

Purpose

To evaluate the association in the change of circulating tumor cell (CTC) levels and clinical outcomes (PFS and OS) in patients with advanced non-small cell lung cancer (NSCLC) treated homogenously with docetaxel and gemcitabine administered every 2 weeks.

Methods

We prospectively evaluated 37 patients for CTC levels at baseline and after 2 months of chemotherapy (before third cycle). Detection was carried out with the CellSearch system.

Results

Nine of the 37 patients (24 %) had ≥2 CTCs at the baseline determination. Median progression-free survival (PFS) was 4.3 months (95 % CI 2.5–8.3) for patients with CTC 0–1 as compared to 9.4 months (95 % CI 1.2–12.2) for those with CTC ≥2 (p = 0.3506). Median overall survival (OS) was 8.1 (95 % CI 2.8–16.3) and 12.2 (95 % CI 1.4–12.2) months for patients with 0–1 CTCs and ≥2 CTCs, respectively (p = 0.7639). Patients with a second CTC quantification were classified as: group 1, CTC = 0–1 at baseline and CTC = 0–1 after second chemotherapy cycle (18 patients); group 2, CTC ≥2 at baseline and CTC = 0–1 after second determination (5 patients). Median PFS was 7.7 and 9.9 months for group 1 and group 2, respectively (p = 0.4467).

Conclusions

CTCs ≥2 at baseline were detected only in 24 % of this group of patients with advanced NSCLC and poor performance status. No significant differences in PFS and OS between patients with or without CTCs at baseline were observed.     

Prognostic score for patients with advanced melanoma treated with ipilimumab

BackgroundImmunotherapies like the cytotoxic T-lymphocyte antigen 4 inhibitor ipilimumab show durable clinical benefit in patients with advanced melanoma. Reliable prognostic markers and risk scores in the era of immunotherapy are still lacking.Patients and methodsWe collected characteristics and outcomes on 134 patients with metastatic melanoma treated with ipilimumab between 2011 and 2014 at a single centre. Cox regression including multivariable fractional polynomials was used to identify independent markers for overall survival (OS). Internal model validation was done using bootstrap procedures.ResultsAfter a median follow-up of 16.1 months the median OS was 7.1 months (95% confidence interval [CI], 6.5–9.8). Nineteen of 134 patients (14.2%) had tumour remissions, 16 partial and 3 complete; 75% had progressive disease. We identified three independent adverse factors for OS: elevated lactate dehydrogenase (LDH) (hazard ratio [HR] 1.03, 95% CI 1.02–1.04), Eastern Cooperative Oncology Group performance status >0 (HR 1.91, 95% CI 1.10–3.30), and number of organs involved (NOI) (HR 1.51, 95% CI 1.22–1.86). To build an easy-to-apply risk score, we dichotomized LDH (>upper limit of normal) and NOI (>2) to built 3 prognostic groups: favourable (no adverse factors, N = 17), intermediate (1 adverse factor, N = 38), and poor prognosis (≥2 adverse factors, N = 73). Respective 12 and 18-month OS for the risk groups were: 85% and 73% (favourable), 41% and 29% (intermediate), and 12% and 6% (poor) (p < 0.001).ConclusionWe propose a simple prognostic score for survival in patients with advanced melanoma treated with ipilimumab using readily available clinical parameters.     

甲胎蛋白对索拉菲尼治疗进展期肝细胞癌的预后评价

近几年来以索拉菲尼为代表的分子靶向药物已成为进展期肝细胞癌综合治疗的热点之一,但目前对于索拉菲尼治疗进展期肝细胞癌的预后评价指标尚没有统一的标准。甲胎蛋白作为重要的肝癌肿瘤标志物,已经广泛地应用于肝细胞癌的筛查诊断,并被认为具有潜在的预测肝细胞癌患者的预后价值。本文总结了近几年来关于甲胎蛋白对索拉菲尼治疗进展期肝细胞癌预后评价的相关文献。从总体上看,甲胎蛋白对于索拉菲尼治疗进展期肝细胞癌预后评价作用是值得肯定的,并可以作为传统的基于影像学资料的肝细胞癌预后评价标准的补充,具有广泛的研究前景和应用价值。     

吉非替尼对晚期非小细胞肺癌患者生活质量的改善

Objective  

The aim of this study was to evaluate the effect of gefitinib on improvement of quality of life (QoL) of patients with advanced non-small cell lung cancer (NSCLC).     

Prognostic factors in advanced metastatic and recurrent melanoma treated with DTIC

Thirty-five patients with recurrent and 25 patients with metastatic malignant melanoma after previous radical locoregional surgery were treated with DTIC at the Institute of Oncology in Kraków between 1976 and 1981. Complete and partial remissions were observed in 19/60, i.e., in 31% of the patients. Our results show an advantage for patients with locoregional recurrence, soft-tissue and lung metastases, provided that the largest deposit is no larger than 5 cm in diameter. There is little chance of remission in patients with liver and bone metastases.     

吉非替尼、厄洛替尼与埃克替尼治疗EGFR基因敏感突变晚期NSCLC患者的疗效观察

目的:观察吉非替尼、厄洛替尼与埃克替尼在EGFR基因敏感突变晚期非小细胞肺癌(NSCLC)患者一线治疗中的疗效差异。方法:收集2013年5月—2014年12月间在我院接受治疗的76例EGFR基因突变的晚期NSCLC患者,随机分为三组,A组接受吉非替尼治疗,250 mg,1次/d,空腹口服;B组接受厄洛替尼治疗,150 mg,1次/d,餐前1 h口服;C组接受埃克替尼治疗,125 mg,3次/d,评价疗效及安全性。结果:吉非替尼组、厄洛替尼组和埃克替尼组的客观有效率（ORR）分别为26.9%、34.6%和45.8%;疾病控制率（DCR）分别为61.5%、73.0%和79.2%。三组之间的有效率和疾病控制率差异无统计学意义(P＞0.05）。三组的无进展生存时间（PFS）分别为9.5个月、10个月和9.5个月;19号外显子缺失突变型患者中,三组的PFS分别为8.5个月、12个月和9个月;21号外显子L858R错义突变型患者中,PFS分别为9.5个月、8.5个月和7个月,三组之间无统计学差异(P＞0.05）。结论:吉非替尼、厄洛替尼与埃克替尼治疗EGFR基因突变的晚期NSCLC疗效相似,但在19号外显子缺失突变型患者中,厄洛替尼略显优势。