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1.
Ning Zhao Xu-chao Zhang Hong-hong Yan Jin-ji Yang Yi-long Wu 《Lung cancer (Amsterdam, Netherlands)》2014
Background
EGFR mutation status is closely related to the efficacy of EGFR-TKIs in advanced non-small cell lung cancer (NSCLC). EGFR-TKIs have become the standard first-line treatment for advanced EGFR-mutation NSCLC, while for EGFR wild-type tumors, the preferred first-line treatment is chemotherapy. However, the efficacy of EGFR-TKIs as second-line treatment in EGFR wild-type NSCLC remains controversial. We sought to evaluate the effectiveness of EGFR-TKI as second-line treatment in EGFR wild-type NSCLC.Methods
Randomized controlled trials that compared EGFR-TKIs with chemotherapy in previously treated advanced NSCLC with wild-type EGFR were included. We performed a meta-analysis to evaluate the effectiveness of EGFR-TKIs compared with standard chemotherapy. The endpoints were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).Results
Six randomized controlled trials with a total of 990 patients with wild-type EGFR were included: 499 in the EGFR-TKIs group and 491 in the chemotherapy group. The results indicated that in the second-line treatment of EGFR wild-type advanced NSCLC, PFS was significantly inferior in the EGFR-TKIs group versus the chemotherapy group (HR = 1.37, 95% CI = 1.20–1.56, P < 0.00001). However, this significant difference did not translate into OS (HR = 1.02, 95% CI = 0.87–1.20, P = 0.81). ORR tended to favor chemotherapy but there was no significant difference compared with EGFR-TKI (RR = 1.77, 95% CI = 0.90–3.50, P = 0.10).Conclusions
Chemotherapy improves PFS significantly but not OS, compared with EGFR-TKIs as a second-line treatment in advanced NSCLC with wild-type EGFR. Whether EGFR-TKIs should be used in EGFR wild-type patients should be considered carefully. 相似文献2.
Tao Jiang Ruirui Cheng Guowei Zhang Chunxia Su Chao Zhao Xuefei Li Jie Zhang Fegnying Wu Xiaoxia Chen Guanghui Gao Wei Li Weijing Cai Fei Zhou Jing Zhao Anwen Xiong Shengxiang Ren Guojun Zhang Caicun Zhou Jun Zhang 《Clinical lung cancer》2017,18(6):631-639.e2
Background
The risk factors for liver metastasis (LM) in patients with non–small-cell lung cancer (NSCLC) remain unknown. Whether LM predicts for the effect of first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutant NSCLC needs to be explored.Patients and Methods
A total of 598 NSCLC patients from 3 centers underwent EGFR testing, and 293 had EGFR-mutant NSCLC. Of the 598 NSCLC patients, 99 had LM; 56 patients with EGFR-mutant NSCLC received EGFR-TKIs as first-line therapy.Results
EGFR mutation was not associated with LM in NSCLC patients (relative ratio, 1.305, P = .261). In the EGFR-mutant group that received first-line EGFR-TKIs, patients with LM had shorter progression-free survival (PFS; 7.5 vs. 11.8 months; P = .0003) and overall survival (OS; 20.8 vs. 30.6 months; P = .0190) than patients without LM. The significant difference in PFS was observed in both patients with EGFR exon 19 deletion (19del) and Leu858Arg mutation (L858R). However, patients with EGFR 19del and LM showed marginally significantly shorter OS (P = .0531) and patients with EGFR L858R and LM had OS similar to that of patients without LM (P = .1883). Regardless of EGFR status, patients with LM who received first-line chemotherapy had PFS and OS similar to those of patients without LM. Univariate analyses identified only never smoking (hazard ratio, 0.536; P = .012) was significantly associated with better OS for patients with NSCLC and LM.Conclusion
EGFR mutation is not an independent risk factor for LM in NSCLC patients. However, the presence of LM is a negative predictive factor for first-line EGFR-TKI therapy for patients with EGFR-mutant NSCLC. 相似文献3.
Irisa K Masago K Togashi Y Fujita S Hatachi Y Fukuhara A Sakamori Y Kim YH Mio T Mishima M 《Medical oncology (Northwood, London, England)》2012,29(1):185-192
A standard, valid assay of comorbidities for elderly patients with advanced non-small-cell lung cancer (NSCLC) who have received
antitumor therapy is needed to provide useful prognostic information. The aim of this study was to analyze prognostic factors
and validate classic Charlson comorbidity index (CCI) and comorbidity scores in elderly patients with advanced NSCLC treated
with chemotherapy or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). A retrospective analysis was
conducted on 162 patients with advanced NSCLC over 70 years old at diagnosis, who were treated with cytotoxic chemotherapy
or with EGFR-TKIs between April 2003 and April 2009 at Kyoto University Hospital. Collected data included clinical assessments,
treatments, toxicities, and outcomes. Survival was estimated using the Kaplan–Meier method. Prognostic factors were evaluated
with log-rank and Cox regression tests. Based on multivariate analysis, unspecified NSCLC histology [Hazard ratio (HR), 1.631;
95% Confidence interval (CI), 1.184–2.263; P = 0.0016], more than 3 comorbidities (HR, 1.317; 95% CI, 1.020–2.675; P = 0.0350), and a CCI of more than 3 (HR, 1.321; 95% CI, 1.031–1.664; P = 0.0285) were significant independent negative prognostic factors for survival. Our results indicate that CCI and the number
of comorbidities are independent predictors of survival in elderly patients undergoing systemic chemotherapy including EGFR-TKIs
for advanced NSCLC. These factors should be taken into consideration in the pretreatment assessment as important factors predicting
survival outcome. 相似文献
4.
Fusako Waki Masashi Ando Atsuo Takashima Kan Yonemori Hiroshi Nokihara Mototaka Miyake Ukihide Tateishi Koji Tsuta Yasuhiro Shimada Yasuhiro Fujiwara Tomohide Tamura 《Journal of neuro-oncology》2009,93(2):205-212
Background Leptomeningeal metastasis (LM) occurs in 4–15% of patients with solid tumors. Although the clinical outcomes in cancer patients
have been improving recently, no standard treatment for LM has been established as yet. The purpose of this study was to identify
the prognostic factors in patients with solid tumors with cytologically proven LM. Methods We retrospectively analyzed a series of 85 consecutive patients with cytologically proven LM who were treated between 1997
and 2005. Results The primary diseases were as follows; lung cancer (n = 36), breast cancer (n = 33), gastric cancer (n = 8), and others (n = 8). Forty-nine patients had brain metastasis at the time of diagnosis of the LM, and in 51 patients, MRI revealed meningeal
dissemination in the brain or spine. The performance status (PS) was 0–1 in 26 patients and 2–4 in 59 patients. Thirty-one
patients, including 19 with breast cancer, four with lung cancer, five with gastric cancer and three with other cancers, were
treated by intrathecal (IT) chemotherapy. The response rate to the IT was 52% (95% confidence interval (CI): 41.4–62.6%).
The median survival was 51 days (range, 3–759 days). A univariate analysis identified breast cancer, good PS (0–1), time to
development of the LM (>1 year), and treatment by IT chemotherapy as being associated with a good prognosis, and multivariate
analysis identified poor PS (HR: 1.72 (95% CI, 1.04–2.86) P = 0.04) and MRI-proven LM (HR: 1.82 (95% CI, 1.11–2.98) P = 0.02) as being associated with a poor prognosis. Conclusion In patients with poor prognostic factors, such as poor PS or MRI-proven LM, palliative therapy might be the most suitable
treatment strategy. 相似文献
5.
Stapleton SL Thompson PA Ou CN Berg SL McGuffey L Gibson B Blaney SM 《Cancer chemotherapy and pharmacology》2008,61(4):647-652
Purpose Valproic acid (VPA), a widely used antiepileptic, also inhibits histone deacetylase (HDAC), and is undergoing evaluation as
an anti-cancer agent. We studied the pharmacokinetics of VPA in the plasma and cerebrospinal fluid (CSF) in a non-human primate
model that is highly predictive of human CSF penetration to determine if levels of VPA required to inhibit HDAC in in vivo
models can be attained.
Methods Oral VPA, 75 mg/kg, was administered to four non-human primates. Serial samples of blood (n = 4) and CSF (n = 3) were obtained for pharmacokinetic studies of total and free VPA. Plasma and CSF VPA concentrations were measured using
the commercially available Abbott AxSYM VPA assay reagent system (Abbott Laboratories, Abbott Park, IL, USA). The resultant
plasma and CSF data were evaluated using pharmacokinetic modeling methods.
Results At a dose of 75 mg/kg, the maximum plasma concentration of VPA was 130.1 ± 70.6 μg/ml (mean ± standard deviation) for total
drug and 53.3 ± 44.4 μg/ml for free drug. The mean plasma area under the curve (AUC) for total drug was 680 ± 233 μg/ml h and for free drug 146 ± 89 μg/ml hr. The maximum CSF concentration occurred 2–3 h after administration and was 28.2 ± 18.6 μg/ml. The CSF AUC for VPA was 108 ± 52 μg/ml h. The CSF penetration of VPA was 12.9 ± 5.1% for total drug and 57.0 ± 8.7% for free drug. Disappearance from the plasma
followed non-linear kinetics with a V
max of 321.2 ± 65.6 μg/kg/min and a K
m of 17.2 ± 13.7 mg/l.
Conclusion Valproic acid deserves further study for the treatment of CNS tumors given its high CSF penetration after oral dosing coupled
with the anti-tumor activity observed in preclinical studies. 相似文献
6.
晚期非小细胞肺癌(NSCLC)的治疗需首先明确其组织学类型与分子学特征。若存在表皮生长因子受体(EGFR)基因突变或渐变性淋巴瘤激酶(ALK)基因融合,应首选分子靶向药物治疗。但分子靶向治疗药物并未改善晚期患者的总生存,如何提高晚期NSCLC患者的总生存是目前临床医生关注的热点。表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)与含铂双药交替使用模式作为晚期NSCLC的一线治疗方案,可能将明显延长EGFR阳性突变患者总生存时间。本文就小分子酪氨酸激酶抑制剂联合化疗治疗NSCLC患者、方式及其疗效的研究进展进行综述。 相似文献
7.
Toth J Egervari K Klekner A Bognar L Szanto J Nemes Z Szollosi Z 《Pathology oncology research : POR》2009,15(2):225-229
Gefitinib and erlotinib are both selective EGFR tyrosine kinase inhibitors (EGFR-TKIs) that have produced responses in a small
subgroup of lung cancer patients. The strongest evidence for a role of EGFR in the biology of glioblastoma stems from clinical
trials in which 15–20% of recurrent glioblastoma patients experienced significant tumour regression in response to these small-molecule
EGFR kinase inhibitors. We examined the protein-kinase domain of the EGFR gene, EGFR protein expression and EGFR gene amplification
in 20 cases of recurrent GBMs. EGFR protein over-expression was found in 65% of cases. EGFR protein over-expression was associated
with EGFR gene amplification in 35% of cases, and with high polysomy in 15% of cases. No mutations were found in the TK domain
of the EGFR gene. Our results confirm that mutations in the kinase domain are absent in recurrent GBM, and this might be a
preponderant factor in the lack of major clinical responses of TKIs in GBM, recent studies have suggested that responsiveness
to EGFR kinase inhibitors was strongly associated with coexpression of EGFRvIII and PTEN. Further prospective validation of
EGFRvIII and PTEN as predictors of the clinical response to EGFR kinase inhibitors in recurrent GBM is strongly anticipated. 相似文献
8.
表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)是具有EGFR基因敏感突变的晚期非小细胞肺癌(NSCLC)患者的一线治疗药物。第一、二代EGFR-TKIs可有效治疗EGFR敏感突变的NSCLC,EGFR第20号外显子的T790M突变是第一、二代EGFR-TKIs的主要耐药机制。以奥西替尼为代表的第三代EGFR-TKIs治疗耐药后出现T790M突变的患者疗效显著,给晚期肺癌患者带来更多的生存获益。然而第三代EGFR-TKIs仍不可避免地出现耐药。本文对第三代EGFR-TKIs治疗晚期NSCLC耐药机制及应对策略的研究进展进行综述。 相似文献
9.
Tao Jiang Qian Chu Huijuan Wang Fei Zhou Guanghui Gao Xiaoxia Chen Xuefei Li Chao Zhao Qinghua Xu Wei Li Fengying Wu Anwen Xiong Jing Zhao Yaping Xu Chunxia Su Shengxiang Ren Caicun Zhou Fred R. Hirsch 《International journal of cancer. Journal international du cancer》2019,144(10):2605-2612
To investigate whether addition of local therapy to EGFR-TKIs could provide survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases (LM). Patients with EGFR-mutant NSCLC and oligometastatic or oligoprogressive LM who met inclusion criteria were retrospectively identified. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and patterns of failure. Addition of local therapy was associated with a significantly longer PFS (13.8 vs. 8.6 m, p <0.001) and OS (31.2 vs. 18.5 m, p <0.001) in whole group. In oligometastatic cohort, 20 patients received EGFR-TKIs and 23 received EGFR-TKIs plus local therapy as first-line treatment. Addition of local therapy showed a significantly longer PFS (12.9 vs. 7.9 m, p = 0.041) and OS (36.8 vs. 21.3 m, p = 0.034) than EGFR-TKIs alone. In oligoprogressive cohort, 24 patients received continuation of EGFR-TKIs plus local therapy and 25 received switching chemotherapy. Median PFS2 (13.9 vs. 9.2 m, p = 0.007) and OS (28.3 vs. 17.1 m, p = 0.011) was significantly longer in combined group than in switching chemotherapy group. Distant metastatic sites progression was the major pattern of failure in combined group while locoregional recurrence was the major reason in monotherapy or switching chemotherapy group. Our study suggested that EGFR-TKIs plus local therapy showed prolonged survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive LM, indicating addition of local therapy would be alternative choice in this clinical scenario. 相似文献
10.
《Journal of thoracic oncology》2021,16(2):250-258
IntroductionPatients with NSCLC with leptomeningeal metastases (LM) presented dismal prognosis. Cerebrospinal fluid (CSF) is suggested as a medium of liquid biopsy of LM. However, the clinical implications of CSF genotyping on treatment outcomes remained elusive.MethodsPatients with EGFR-mutated advanced NSCLC with LM were included: cohort 1, patients with LM who were treated with osimertinib with CSF and plasma genotyping performed before the first dosing of osimertinib (baseline, n = 45); cohort 2, CSF genotyping on progression on osimertinib and development of LM (the progression event on osimertinib is the diagnosis of LM, n = 35). Circulating tumor DNA in CSF underwent next-generation sequencing.ResultsSensitivity of CSF genotyping for EGFR-sensitizing mutations was 93.3% (42 of 45) and 97.1% (34 of 35) in cohorts 1 and 2, respectively. In cohort 1, patients with EGFR exon 19 deletion had higher median intracranial progression free survival (iPFS) than those with EGFR exon 21 L858R mutation (11.9 versus 2.8 mo; p = 0.02). Median iPFS was significantly longer in patients with T790M-positive CSF genotyping (15.6 mo) than T790M-negative CSF (7.0 mo, p = 0.04). Concurrent CDK4 (2.8 versus 11.6 mo, p = 0.002) and CDKN2A (2.5 versus 9.6 mo, p = 0.04) mutation with EGFR-sensitizing mutations indicated lower median iPFS. Patients with T790M-negative CSF, EGFR exon 21 L858R mutation, concurrent FGF3 alteration, and over first-line osimertinib had shortened iPFS. In cohort 2, possible EGFR-related and EGFR-independent resistance mechanisms were found including C797S mutation, MET dysregulation, and TP53 plus RB1 co-occurrence. Patients with loss of T790M in CSF had a shorter median iPFS (7.4 mo) compared with those with reserved T790M (13.6 mo, p = 0.01).ConclusionsGenotyping of CSF indicated heterogeneous response to osimertinib and revealed the genetic characteristic of LM on osimertinib failure in patients with EGFR-mutated NSCLC diagnosed with LM. 相似文献
11.
Somatic mutations of epidermal growth factor receptor (EGFR) are the strongest predictive markers for the response to EGFR-tyrosine kinase inhibitors (TKIs). Patients with EGFR mutations generally receive EGFR-TKI treatment, and their survival has been significantly improved compared with that before the development of EGFR-TKIs. This study aimed to clarify the impact of EGFR mutational status on the survival of patients with non-small cell lung cancer (NSCLC) receiving cytotoxic agents, but not EGFR-TKIs, as their first-line chemotherapy. In addition, we analyzed patients with EGFR mutations to determine whether the timing of EGFR-TKI administration affects overall survival (OS). A total of 83 NSCLC patients with stage IIIB/IV who received chemotherapy alone and whose EGFR mutational status was known were investigated. Univariate and multivariate analysis for OS was performed using parameters such as age, gender, performance status (PS), histology, disease stage, smoking status, EGFR mutational status and administration of a first-line regimen. Among the 52 patients with EGFR mutations who received EGFR-TKIs, OS between those who received EGFR-TKIs as their first-line treatment and after chemotherapy were similar. Among the 83 patients who received cytotoxic agents as their first-line chemotherapy, the multivariate analysis showed OS to be significantly associated with PS (p<0.001), histology (p=0.039) and EGFR mutational status (p=0.040). OS was almost similar among the 52 patients with EGFR mutations who received EGFR-TKIs in a first- and second-line setting (25.6 vs. 26.8 months, p=0.914). The EGFR mutational status had a significant impact on the survival of NSCLC patients, although these patients did not receive EGFR-TKIs as their first-line chemotherapy. In future randomized trials, even when EGFR-TKIs are not included in experimental regimens, patients may need to be stratified by EGFR mutational status in order that study results be evaluated appropriately. 相似文献
12.
H. Nakagawa Toshiaki Fujita Shigeki Kubo Koji Tokiyoshi Masanobu Yamada Takuji Kanayama Yasushi Hagiwara Hiroshi Nakanomyo Masaki Hiraoka 《Cancer chemotherapy and pharmacology》1996,37(4):317-326
Platinum (Pt) levels in plasma and cerebrospinal fluid (CSF) in patients with malignant glioma were determined after initiation
of selective intraarterial chemotherapy with a combination of VP-16 (etoposide) and CDDP (cisplatin), and were compared with
the CSF Pt levels in patients with metastatic brain tumors after intravenous or intracarotid administration of VP-16 and CDDP.
CSF Pt levels were also compared for various administration routes, doses, CSF sampling routes and blood–CSF barriers in metastatic
brain tumor. Changes in the blood-CSF barrier to CDDP during treatment in a patient with meningeal lymphoma and in a patient
recovering from surgical removal of a metastatic brain tumor were also examined by periodic administration of CDDP. All CSF
samples were taken through Ommaya reservoirs placed in the anterior horn of the lateral ventricle or the postoperative cavity.
The mean peak CSF/plasma total Pt ratio (T/T ratio) and the mean CSF total Pt/plasma ultrafiltrable Pt ratio (T/U ratio) were
highest (15.0% and 24.4%, respectively) following selective intraarterial infusion of CDDP in patients with malignant glioma,
followed by intravenous infusion in meningeal carcinomatosis (11.5% and 18.9%), intracarotid administration (5.4% and 8.7%)
and intravenous infusion (60 mg/m2 2.5% and 100 mg/m2 2.9%; and 60 mg/m2 3.5% and 100 mg/m2 7.7%) in patients with the solid type of metastatic brain tumor. In CSF obtained from the postoperative cavity in cases of
metastatic brain tumor, T/T and T/U ratios were extremely high (40.9% and 62.4%). However, the CSF Pt level even after selective
intraarterial administration of CDDP in malignant glioma was 0.51–1.64 μg/ml total Pt and 0.43–1.08 μg/ml ultrafiltrable Pt.
Even the CSF level obtained from the postoperative cavity was 1.0–4.7 μg/ml total Pt. These low levels of total and ultrafiltrable
Pt are considered not to be cytotoxic to disseminated cells in the CSF space and to normal brain cells. As for changes in
the blood–CSF barrier, repeated administration of CDDP showed that the rate of entry of Pt into the CSF decreased in parallel
with improvements apparent on CT scans in the patient with meningeal lymphoma, and also showed that the blood–CSF barrier
to Pt was gradually repaired after the metastatic brain tumor had been removed.
Received: 20 June 1994/Accepted: 14 May 1995 相似文献
13.
《Lung cancer (Amsterdam, Netherlands)》2015,88(3):311-317
ObjectivesExpression of insulin-like growth factor 1 receptor (IGF-1R) in non-small cell lung cancer (NSCLC) is associated with poor prognosis. The IGF-1R pathway activates downstream targets that bypass dependency in signals from the epidermal growth factor receptor (EGFR), which mediates resistance to EGFR tyrosine kinase inhibitors (TKIs). The aim of the present study was to determine the predictive role of IGF-1R expression in the response to EGFR-TKIs of NSCLC patients harboring activating EGFR mutations.Materials and methodsWe retrospectively studied 62 NSCLC patients who had activating EGFR mutations and received TKIs. Protein expression of IGF-1R, vascular endothelial growth factor (VEGF), and human epidermal growth factor receptor 2 (HER2) were measured by immunohistochemical staining. Univariate and multivariate analyses were performed to identify predictive factors associated with the responses to EGFR-TKIs. The relationship of progression-free survival (PFS) with IGF-1R expression and the presence of diabetes mellitus (DM) were examined.ResultsOf 62 EGFR mutation positive patients, 26 expressed IGF-1R, and 13 had DM. In the multivariate analysis, young age, squamous cell carcinoma, and IGF-1R expression were independently associated with a shorter PFS after treatment with EGFR-TKIs. Patients expressing IGF-1R showed a significantly shorter PFS in response to EGFR-TKIs compared with those lacking IGF-1R expression (9.1 vs. 20.1 months, p = 0.005). The 13 patients with DM were more likely to express IGF-1R (p = 0.001) and had shorter PFS times when treated with first-line EGFR-TKIs (7.6 vs. 18.6 months, p = 0.005), compared with those without DM.ConclusionIGF-1R expression was a negative predictive factor for a response to EGFR-TKIs in NSCLC patients harboring activating EGFR mutations. Moreover, patients with DM highly expressed IGF-1R in tumor tissues, which was associated with a poor response to first-line TKI therapy. Further studies aimed at overcoming EGFR-TKI resistance will need to also address IGF-1R pathways. 相似文献
14.
Okamoto I Mitsudomi T Nakagawa K Fukuoka M 《Therapeutic advances in medical oncology》2010,2(5):301-307
Gefitinib and erlotinib, small-molecule tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), were the first molecularly targeted agents to become clinically available for the treatment of non-small cell lung cancer (NSCLC). During the course of their clinical development, it has become clear that the substantial clinical benefit associated with EGFR-TKIs is limited to patients harboring activating mutations of EGFR. Accumulating clinical outcomes in patients with EGFR mutation-positive NSCLC treated with EGFR-TKIs support the notion that this group of individuals constitutes a clinically distinct population. These findings have prompted investigations of the potential role of first-line treatment with EGFR-TKIs in molecularly selected patients, with platinum-based doublet chemotherapy currently being the standard of care for most individuals with advanced NSCLC. This review summarizes the results of recent clinical trials of EGFR-TKIs in selected patients and highlights the efficacy of these drugs in first-line treatment as a form of personalized medicine aimed at improving therapy for advanced NSCLC. 相似文献
15.
Grandin L Orsi L Troussard X Monnereau A Berthou C Fenaux P Marit G Soubeyran P Huguet F Milpied N Leporrier M Hemon D Clavel J 《Cancer causes & control : CCC》2008,19(3):305-315
Objectives Investigating the relationship between skin type, UV exposure, and lymphoid malignancies (LM).
Methods We conducted a hospital-based case–control study in France, including 813 incident cases of non-Hodgkin’s lymphoma (NHL),
Hodgkin’s lymphoma (HL), lymphoproliferative syndrome (LPS) or multiple myeloma and 748 controls.
Results Positive associations between HL and blond/red hair (OR = 1.8 [0.8–3.8]), very fair/fair skin (OR = 1.6 [1.0–2.5]) were observed.
High propensity to burn was associated with HL (OR = 1.5 [1.0–2.2]) and LPS (OR = 1.4 [1.0–2.1]). Poor ability to tan was
significantly associated with HL (OR = 1.7 [1.0–2.8]). Having light hair with high propensity to burn was associated with
NHL (OR = 1.5 [0.9–2.5]) and significantly with HL (OR = 3.4 [1.4–8.4]). Having dark hair with high propensity to burn was
significantly associated with LPS (OR = 1.5 [1.0–2.2]). The associations with HL and NHL were significant for men only, with
significant interactions. Outdoors activities since leaving school or in the last decade were not related to LM. Only an almost
negative trend was observed. Prior exposure to artificial UV was not associated with LM.
Conclusion These results suggest a positive association between the most reactive and palest skin types and NHL or HL in men and do not
rule out a slight negative relationship between UV exposure and LM. 相似文献
16.
Objective
To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in molecularly selected patients with advanced non-small cell lung cancer (NSCLC), we performed this pooled analysis.Method
Randomized trials of EGFR-TKIs as treatment for advanced NSCLC were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of EGFR-TKIs in the selected patients by EGFR-mutation status were calculated.Results
Out of 2134 retrieved articles, 30 randomized controlled trials (RCTs) enrolling more than 4053 patients with wild-type EGFR tumors and 1592 patients with mutant EGFR tumors were identified. For EGFR mutant patients, EGFR-TKIs treatment improved progression-free survival (PFS) compared with chemotherapy: the summary HRs were 0.41 (p?<?0.00001) for the first-line setting and 0.46 (p?=?0.02) for second/third-line setting, respectively. Also, the same superior trend was found with TKIs maintenance over placebo (HR?=?0.14, p?<?0.00001) and with TKIs combined with chemotherapy over chemotherapy (HR?=?0.49, p?=?.002) in both the first-line and maintenance therapy settings. For EGFR wild-type patients, EGFR-TKIs have fared worse than chemotherapy in the first-line setting (HR?=?1.65, p?=?.03) and in the second/third-line setting (HR?=?1.27, p?=?.005). However, EGFR-TKIs maintenance still produced a reduction of 19 % in the risk of progression over placebo (HR?=?0.81, p?=?.02). Furthermore, EGFR-TKIs added to chemotherapy as first-line treatment resulted in an improvement of PFS over chemotherapy alone in such wild-type EGFR patients (HR?=?0.82, p?=?.03). In overall survival (OS) analysis, only EGFR-TKIs single agent was inferior to chemotherapy in EGFR wild-type patients (HR?=?1.13, p?=?.02). No statistically significant difference in terms of OS was observed in any other subgroup analysis.Conclusions
For EGFR mutant patients, EGFR-TKIs therapy produced a prominent PFS benefit in all settings. Among EGFR wild-type patients, EGFR-TKIs were inferior to chemotherapy both for first-line treatment and for second/third-line treatment. However, EGFR-TKIs maintenance and addition of EGFR-TKIs to chemotherapy could provide additive benefit over chemotherapy alone in such EGFR wild-type patients.17.
Kijima T Suzuki M Ueda K Minami S Takeda Y Goya S Matsuoka H Kumagai T Yoshida M Osaki T Tachibana I Yokota S Kawase I 《Oncology research》2007,16(10):489-495
The tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) gefitinib has beneficial effect in some patients with refractory advanced non-small cell lung cancer (NSCLC). However, the majority of responders eventually develop acquired resistance during the course of prolonged continuous treatment. Here we present a case of 76-year-old Japanese female, who had never smoked, with poor performance status from bronchioloalveolar carcinoma (BAC), in whom a brief initial 5-week administration of gefitinib resulted in dramatic antitumor effects that lasted approximately 8.5 months after cessation of the treatment. Furthermore, the relapsed tumor later regressed again by re-treatment with the TKI. She survived 26 months since she first took gefitinib. Unexpectedly, neither sensitizing mutations for EGFR-TKIs nor increased copy numbers were detected in EGFR gene of her BAC cells. This case suggests that, in some patients with NSCLC, even short-term administration of gefitinib may bring about clinical benefits and disease response comparable to the standard long-term daily dosing schedule. Short-term use of gefitinib will also be able to minimize the expensive medical cost of the TKI. The potential role of short-term or pulse-dose therapy with EGFR-TKIs should be clarified in further prospective studies. Moreover, it is urgent to develop better strategies by which we could distinguish responders to the TKIs from nonresponders among patients who do not have any EGFR gene alterations. 相似文献
18.
F Wang S Wang Z Wang J Duan T An J Zhao H Bai J Wang 《Journal of experimental & clinical cancer research : CR》2012,31(1):65
ABSTRACT: BACKGROUND: EGFR mutation is a strong predictive factor of EGFR-TKIs therapy. However, at least 10% of patients with EGFR wild-type are responsive to TKIs, suggesting that other determinants of outcome besides EGFR mutation might exist. We hypothesized that activation of phosphorylated EGFR could be a potential predictive biomarker to EGFR-TKIs treatment among patients in wild-type EGFR. METHOD: Total of 205 stage IIIb and IV NSCLC patients, tissue samples of whom were available for molecular analysis, were enrolled in this study. The phosphorylation of EGFR at tyrosine 1068 (pTyr1068) and 1173 (pTyr1173) were assessed by immunohistochemistry, and EGFR mutations were detected by denaturing high performance liquid chromatograph (DHPLC). RESULTS: Among 205 patients assessable for EGFR mutation and phosphorylation analysis, 92 (44.9%) were EGFR mutant and 165 patients (57.6%) had pTyr1173 expression. Superior progression-free survival (PFS) was seen after EGFR-TKIs therapy in patients with pTyr1068 expression compared to pTyr1068 negative ones (median PFS 7.0 months vs. 1.2 months, P<0.001). Inversely, patients with pTyr1173 had a shorter PFS (4.8 months VS. 7.7 months, P=0.016). In subgroup of patients with wild-type EGFR, pTyr1068 expression positive ones had a significantly prolonged PFS (4.2 months vs.1.2 months P<0.001) compared with those without pTyr1068 expression.Sixteen patients with both wild-type EGFR and pTyr1068 who responded to EGFR-TKIs had median PFS of 15.6 months (95%CI: 7.28-23.9). CONCLUSION: pTyr1068 may be a predictive biomarker for screening the population for clinical response to EGFR-TKIs treatment; especially for patients with wild-type EGFR. 相似文献
19.
表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors, EGFR-TKI)在晚期EGFR突变阳性的非小细胞肺癌(non-small cell lung cancer, NSCLC)患者中的疗效肯定,但EGFR-TKI能否提高完全切除的NSCLC术后辅助治疗疗效不确切。部分研究发现在可切除的Ⅰ~Ⅲ期EGFR敏感突变肺腺癌患者中,辅助TKI治疗有使无疾病生存(disease free survival,DFS)获益的趋势,另一部分临床研究未能证实EGFR-TKI在术后辅助治疗有获益。造成各研究结果不一的原因很多,如人群选择、EGFR-TKI使用时长、耐药等。国内外目前一些设计比较合理的,对比EGFR-TKI化疗辅助治疗Ⅱ~ⅢA期EGFR敏感突变的NSCLC临床研究正在进行,值得期待。目前,早期NSCLC术后TKI辅助治疗仅限于临床试验,不建议作为临床常规治疗。 相似文献
20.
First-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib and erlotinib, have proven to be highly effective agents for advanced non-small cell lung cancer (NSCLC) in patients harboring an activating EGFR mutation such as the exon 19 deletion mutation and L858R. Although those reversible small molecular targeted agents provide a significant response and survival benefit, all responders eventually acquire resistance. Second-generation EGFR-targeting agents, such as irreversible EGFR/HER2 tyrosine kinase inhibitors and pan-HER TKIs, may improve survival further and be useful for patients who acquired resistance to first-generation EGFR-TKIs. This review discusses novel therapeutic strategies for EGFR-mutated advanced NSCLC using first- and second-generation EGFR-TKIs. 相似文献