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1.
Yun Chiang James Chih-Hsin Yang Feng-Ming Hsu Yu-Hsuan Chen Jin-Yuan Shih Zhong-Zhe Lin Keng-Hsueh Lan Ann-Lii Cheng Sung-Hsin Kuo 《PloS one》2015,10(12)
Background and Purpose
For metastatic non-small cell lung cancer (NSCLC) patients with controlled extrathoracic disease after systemic treatment, stable or progressive primary lung lesions may cause respiratory symptoms and increase comorbidities. In the present study, we sought to investigate whether aggressive palliative thoracic radiotherapy (RT) can enhance local control and improve the survival for this subgroup of patients.Materials and Methods
Between March 2006 and December 2014, 56 patients with metastatic NSCLC who had responsive or stable extrathoracic diseases after chemotherapy and/or molecular targets, and received thoracic RT for stable and progressive primary lung lesions were included. RT with a median dose of 55 Gy (range, 40–62 Gy) was administered in 1.8–2.5 Gy fractions to primary lung tumor and regional mediastinal lymph nodes using modern RT technique. Overall survival (OS) from diagnosis, and locoregional progression-free survival (LRPFS), and survival calculated from radiotherapy (OS-RT) were estimated using the Kaplan-Meier method.Results
There were 37 men and 19 women with a median age of 60 years at diagnosis. The median interval from the diagnosis of metastatic disease to thoracic RT was 8 months. Following thoracic RT, 26 patients (46%) achieved complete or partial response (overall response rate, ORR). Patients with squamous cell carcinoma or poorly-differentiated carcinoma had a higher ORR than those with adenocarcinoma (63% vs. 34%, P = 0.034). EGFR mutations was closely associated with a better ORR (45% vs. 29%, P = 0.284). At a median follow-up time of 44 months, the median OS, LRPFS after RT, and OS-RT were 50 months, 15 months, and 18 months.Conclusion
Radical palliative throractic RT is safe and might be beneficial for primary lung lesions of metastatic NSCLC patients with controlled extrathoracic diseases. 相似文献2.
Background
Currently, the standard treatment for newly diagnosed glioblastoma multiforme (GBM) is maximal safe surgical resection followed by radiation therapy with concurrent and adjuvant temozolomide. However, disease recurs in almost all patients, and the optimal salvage treatment for recurrent GBM remains unclear. We conducted a systematic review and meta-analysis of published clinical trials to assess the efficacy and toxicities of angiogenesis inhibitors alone as salvage treatment in these patients.Methods
Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). Demographic data, treatment regimens, objective response rate (ORR), median progression-free survival (PFS), median overall survival (OS), 6-months PFS rate, 1-year OS and grade 3/4 toxicities were extracted. We also compared the main outcomes of interest between bevacizumab and other angiogenesis inhibitors. All analyses were performed using Comprehensive Meta Analysis software (Version 2.0).Results
A total of 842 patients were included for analysis: 343 patients were treated with bevacizumab, 386 with other angiogenesis inhibitors and 81 with thalidomide. The pooled ORR, 6-months PFS, and 1-year OS for recurrent GBM patients receiving angiogenesis inhibitors was 20.1%, 19.5% and 29.3%, respectively. The use of single agent bevacizumab in recurrent GBM significantly improved ORR and 6-months PFS when compared to other angiogenesis inhibitors [relative risk (RR) 2.93, 95% CI 1.38–6.21; p = 0.025; and RR 2.36 95% CI 1.46–3.82; p<0.001, respectively], while no significant difference in 1-year OS was found between the two groups (p = 0.07). when compared to thalidomide, bevacizumab treatment in recurrent GBM significantly improved ORR (RR 6.8, 95%CI: 2.64–17.6, p<0.001), but not for 6-months PFS (p = 0.07) and 1-year OS (p = 0.31). As for grade 3/4 toxicities, the common toxicity was hypertension with pooled incidence of 12.1%, while high-grade thromboembolic events (2.2%), hemorrhage (5.1%) and GI perforation (2.8%) associated with angiogenesis inhibitors were relatively low.Conclusions
In comparison with other angiogenesis inhibitors and thalidomide, the use of single agent bevacizumab as salvage treatment for recurrent GBM patients improve ORR and 6-months PFS, but not for 1-year OS. 相似文献3.
Jennifer Ho John Ondos Holly Ning Sharon Smith Teri Kreisl Fabio Iwamoto Joohee Sul Lyndon Kim Kate McNeil Andra Krauze Uma Shankavaram Howard A. Fine Kevin Camphausen 《PloS one》2013,8(8)
Purpose
Standard treatment for glioblastoma (GBM) is surgery followed by radiation (RT) and temozolomide (TMZ). While there is variability in survival based on several established prognostic factors, the prognostic utility of other factors such as tumor size and location are not well established.Experimental Design
The charts of ninety two patients with GBM treated with RT at the National Cancer Institute (NCI) between 1998 and 2012 were retrospectively reviewed. Most patients received RT with concurrent and adjuvant TMZ. Topographic locations were classified using preoperative imaging. Gross tumor volumes were contoured using treatment planning systems utilizing both pre-operative and post-operative MR imaging.Results
At a median follow-up of 18.7 months, the median overall survival (OS) and progression-free survival (PFS) for all patients was 17.9 and 7.6 months. Patients with the smallest tumors had a median OS of 52.3 months compared to 16.3 months among patients with the largest tumors, P = 0.006. The patients who received bevacizumab after recurrence had a median OS of 23.3 months, compared to 16.3 months in patients who did not receive it, P = 0.0284. The median PFS and OS in patients with periventricular tumors was 5.7 and 17.5 months, versus 8.9 and 23.3 months in patients with non-periventricular tumors, P = 0.005.Conclusions
Survival in our cohort was comparable to the outcome of the defining EORTC-NCIC trial establishing the use of RT+TMZ. This study also identifies several potential prognostic factors that may be useful in stratifying patients. 相似文献4.
Wei-Xiang Qi Qiong Wang Yan-Ling Jiang Yuan-Jue Sun Li-na Tang Ai-na He Da-liu Min Feng Lin Zan Shen Yang Yao 《PloS one》2013,8(2)
Background
Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC), but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC.Methods
Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.Results
Eight eligible trials involved 2417 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that combining targeted therapy significantly improved OS (HR 0.90, 95%CI: 0.82–0.99, p = 0.024), PFS (HR 0.83, 95%CI: 0.72–0.97, p = 0.018), and ORR (OR 1.35, 95%CI 1.01–1.80, P = 0.04). Sub-group analysis based on phases of trials, EGFR-status and KRAS status also showed that there was a tendency to improve PFS and OS in combining targeted therapy, except that PFS for patients with EGFR-mutation or wild type KRAS favored erlotinib monotherapy. Additionally, more incidence of grade 3 or 4 rash, fatigue and hypertension were observed in combining targeted therapy.Conclusions
With the available evidence, combining targeted therapy seems superior over erlotinib monotherapy as second-line treatment for advanced NSCLC. More studies are still needed to identify patients who will most likely benefit from the appropriate combining targeted therapy. 相似文献5.
Background
Evidence on the benefits of combining cyclooxygenase-2 inhibitor (COX-2) in treating non-small cell lung cancer (NSCLC) is still controversial. We investigated the efficacy and safety profile of cyclooxygenase-2 inhibitors in treating NSCLC.Methods
The first meta-analysis of eligible studies was performed to assess the effect of COX-2 inhibitors for patients with NSCLC on the overall response rate (ORR), overall survival (OS), progression-free survival (PFS), one-year survival, and toxicities. The fixed-effects model was used to calculate the pooled RR and HR and between-study heterogeneity was assessed. Subgroup analyses were conducted according to the type of COX-2 inhibitors, treatment pattern, and treatment line.Results
Nine randomized clinical trials, comprising 1679 patents with NSCLC, were included in the final meta-analysis. The pooled ORR of patients who have NSCLC with COX-2 inhibitors was significantly higher than that without COX-2 inhibitors. In subgroup analysis, significantly increased ORR results were found on celecoxib (RR = 1.29, 95% CI: 1.09, 1.51), rofecoxib (RR = 1.61, 95% CI: 1.14, 2.28), chemotherapy (RR = 1.40, 95% CI: 1.20, 1.63), and first-line treatment (RR = 1.39, 95% CI: 1.19, 1.63). However, COX-2 inhibitors had no effect on the one-year survival, OS, and PFS. Increased RR of leucopenia (RR = 1.21, 95% CI: 1.01, 1.45) and thrombocytopenia (RR = 1.36, 95% CI: 1.06, 1.76) suggested that COX-2 inhibitors increased hematologic toxicities (grade ≥ 3) of chemotherapyConclusions
COX-2 inhibitors increased ORR of advanced NSCLC and had no impact on survival indices, but it may increase the risk of hematologic toxicities associated with chemotherapy. 相似文献6.
Background
Lung cancer, particularly non-small-cell lung cancer (NSCLC) is the leading cause of cancer mortality. Chemotherapy combined dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) immunotherapy has been applied in advanced NSCLC patients'' treatment, but couldn''t provide consistent beneficial results. Therefore, it is necessary to evaluate the efficiency and safety of combination therapy to promote the application.Methods
A literature search for randomized controlled trials of NSCLC was conducted in PubMed database. Before meta-analysis was performed, studies were evaluated heterogeneity. Pooled risk ratios (RRs) were estimated and 95% confidence intervals (CIs) were calculated using a fixed-effect model. Sensitivity analysis was also performed.Results
Six eligible trials were enrolled. Efficiency and safety of chemotherapy followed by DC-CIK immunotherapy (experimental group) and chemotherapy alone (control group) were compared. 1-year overall survival (OS) (P = 0.02) and progression free survival (PFS) (P = 0.005) in the experimental group were significantly increased compared with the control. Disease control rate (DCR) (P = 0.006) rose significantly in experimental group. However, no significant differences between the two groups were observed in 2-year OS (P = 0.21), 2-year PFS (P = 0.10), overall response rate (ORR) (P = 0.76) and partial response (PR) (P = 0.22). Temporary fever, anemia, leukopenia and nausea were the four major adverse events (AEs) treated by chemotherapy. The incidence of anemia, leukopenia and nausea in the experimental group was obviously lower than the control group. Temporary fever rate was higher in experimental group than that in the control, but could be alleviated by taking sufficient rest.Conclusions
Chemotherapy combined with DC-CIK immunotherapy showed superiority in DCR, 1-year OS and PFS, and no more AEs appeared, however, there was no significant improvement in ORR, PR, 2-year OS and PFS. As a whole, the combination therapy is safer but modest in efficacy for advanced NSCLC patients. 相似文献7.
Background
The combination of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC). This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.Methods
EMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL), Chinese biomedical literature database (CNKI) and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.Results
A total of six randomized controlled trials (RCTs) including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS), time to progression (TTP) and objective response rate (ORR), compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98–1.12; TTP: HR = 0.94, 95%CI = 0.89–1.00; ORR: RR = 1.07, 95%CI = 0.98–1.17), and no significant difference in OS and progression-free survival (PFS), compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83–1.46; PFS: HR = 0.86, 95% CI = 0.67–1.10). The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10–1.79) and rash (RR = 7.43, 95% CI = 4.56–12.09), compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25–35.93) and fatigue (RR = 9.60, 95% CI = 2.28–40.86) compared with EGFR TKI monotherapy.Conclusions
The synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC. 相似文献8.
Wenhua Liang Xuan Wu Shaodong Hong Yaxiong Zhang Shiyang Kang Wenfeng Fang Tao Qin Yan Huang Hongyun Zhao Li Zhang 《PloS one》2014,9(10)
Background
Multi-targeted antiangiogenic tyrosine kinase inhibitors (MATKIs) have been studied in many randomized controlled trials (RCTs) for treatment of advanced non-small cell lung cancer (NSCLC). We seek to summarize the most up-to-date evidences and perform a timely meta-analysis.Methods
Electronic databases were searched for eligible studies. We defined the experimental arm as MATKI-containing group and the control arm as MATKI-free group. The extracted data on objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS) and overall survival (OS) were pooled. Subgroup and sensitivity analyses were conducted.Results
Twenty phase II/III RCTs that involved a total of 10834 participants were included. Overall, MATKI-containing group was associated with significant superior ORR (OR 1.29, 95% CI 1.08 to 1.55, P = 0.006) and prolonged PFS (HR 0.83, 0.78 to 0.90, P = 0.005) compared to the MATKI-free group. However, no significant improvements in DCR (OR 1.08, 1.00 to 1.17, P = 0.054) or OS (HR 0.97, 0.93 to 1.01, P = 0.106) were observed. Subgroup analyses showed that the benefits were predominantly presented in pooled results of studies enrolling previously-treated patients, studies not limiting to enroll non-squamous NSCLC, and studies using MATKIs in combination with the control regimens as experimental therapies.Conclusions
This up-to-date meta-analysis showed that MATKIs did increase ORR and prolong PFS, with no significant improvement in DCR and OS. The advantages of MATKIs were most prominent in patients who received a MATKI in combination with standard treatments and in patients who had previously experienced chemotherapy. We suggest further discussion as to the inclusion criteria of future studies on MATKIs regarding histology. 相似文献9.
Pei-Jing Li Ting Jin Dong-Hua Luo Ting Shen Dong-Mei Mai Wei-Han Hu Hao-Yuan Mo 《PloS one》2015,10(10)
Purpose
To estimate the influence of prolonged radiation treatment time (RTT) on survival outcomes in nasopharyngeal carcinoma after continuous intensity-modulated radiation therapy.Methods and Materials
Retrospectively review 321 patients with NPC treated between October 2009 and December 2010 and all of them underwent simultaneous accelerated intensity-modulated radiation therapy. The fractionated dose was 2–2.47 Gy/F (median 2.27 Gy), and the total dose for nasopharyngeal region was 64–74 Gy/ 28–33 fractions. The association of prolonged RTT and treatment interruption with PFS, LRFS and DFFS were assessed by univariate analysis and multivariate analysis. Survival analyses were carried out using Kaplan–Meier methodology and the log-rank test was used to assess the difference. The Cox regression proportional hazard model was used for multivariate analyses and evaluating the prognostic parameters for PFS, LRFS and DFFS.Results
Univariate analysis revealed no significant associations between prolonged RTT and PFS, LRFS, DFFS when dichotomized using various cut-off values (all P>0.05). In multivariate analysis, RTT (range, 36–63 days) as a continuous variable, had no influence on any survival outcome as well (P>0.05). T and N classification were independent prognostic factors for PFS, LRFS and DFFS (all P<0.05, except T classification for LRFS, P = 0.057). Age was an independent prognostic factor for PFS (hazard ratio [HR], 1.033; P = 0.008) and DFFS (HR, 1.032; P = 0.043).Conclusion
We conclude that no such association between survival outcomes and radiation treatment duration (range: 36–63 days) can be found in the present retrospective study, however, we have to remind that prolongation in treatment should be limited in clinical application and interruptions caused by any reason should be minimized as much as possible. 相似文献10.
Background
Gemcitabine (GEM) is the standard first-line chemotherapy that provides limited clinical benefits for patients with locally advanced/metastatic pancreatic adenocarcinoma (LA/MPC). However, the fluorouracil derivatives (CAP and S-1) show promising efficacy in these patients. This study compared the efficacy and safety of GEM with GEM plus fluorouracil drugs in the treatment of LA/MPC.Methods
Pubmed, EMBASE and Cochrane Library databases were searched for relevant randomized controlled trials published on or before January 2014. The Cochrane Collaboration''s tool was used to assess the risk of bias in randomized trials. The primary end point was overall survival (OS); the secondary end points were one-year survival rate, objective response rate (ORR) and toxicity rates (TRs).Results
A total of 8 randomized controlled trials involving 2,126 patients were included in the systematic evaluation. The results showed that OS was significantly improved (HR 0.83, P<0.01; HR 0.87, P = 0.03; HR 0.80, P = 0.01; respectively) and ORR was significantly increased (OR 0.51, P<0.01; OR 0.66, P = 0.03; OR 0.35, P<0.01; respectively) in the GEM+5-FU/CAP/S-1, GEM+CAP and GEM+S-1 groups compared to the GEM alone group. In addition, the one-year survival rate was significantly increased (OR 0.78 P = 0.01; OR 0.47, P = 0.04; respectively) in the GEM+5-FU/CAP/S-1 and GEM+S-1 groups compared to the GEM alone group. The frequency of grade 3/4 TRs were higher in GEM+5-FU/CAP/S-1 group, the significant increase of grade 3/4 neutropenia, thrombocytopenia and diarrhea were observed.Conclusions
GEM combined with fluorouracil drugs significantly improved OS and increased one-year survival rate and ORR compared to GEM alone in LA/MPC patients. GEM combined with fluorouracil drugs may be considered as an acceptable alternative treatment for LA/MPC patients. 相似文献11.
Qingbin Li Baoshi Chen Jinquan Cai Ying Sun Guangzhi Wang Yongli Li Ruiyan Li Yan Feng Bo Han Jianlong Li Yu Tian Liye Yi Chuanlu Jiang 《PloS one》2016,11(3)
Background
Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ chemotherapy is the current standard of care for patients with GBM. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are key modulators of tumor invasion and metastasis due to their ECM degradation capacity. The aim of the present study was to identify the most informative MMP member in terms of prognostic and predictive ability for patients with primary GBM.Method
The mRNA expression profiles of all MMP genes were obtained from the Chinese Glioma Genome Atlas (CGGA), the Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the GSE16011 dataset. MGMT methylation status was also examined by pyrosequencing. The correlation of MMP9 expression with tumor progression was explored in glioma specimens of all grades. Kaplan–Meier analysis and Cox proportional hazards regression models were used to investigate the association of MMP9 expression with survival and response to temozolomide.Results
MMP9 was the only significant prognostic factor in three datasets for primary glioblastoma patients. Our results indicated that MMP9 expression is correlated with glioma grade (p<0.0001). Additionally, low expression of MMP9 was correlated with better survival outcome (OS: p = 0.0012 and PFS: p = 0.0066), and MMP9 was an independent prognostic factor in primary GBM (OS: p = 0.027 and PFS: p = 0.032). Additionally, the GBM patients with low MMP9 expression benefited from temozolomide (TMZ) chemotherapy regardless of the MGMT methylation status.Conclusions
Patients with primary GBMs with low MMP9 expression may have longer survival and may benefit from temozolomide chemotherapy. 相似文献12.
Yuri Jeong Sang Min Yoon Seungbong Han Ju Hyun Shim Kang Mo Kim Young-Suk Lim Han Chu Lee So Yeon Kim Jin-hong Park Sang-wook Lee Seung Do Ahn Eun Kyung Choi Jong Hoon Kim 《PloS one》2015,10(8)
Background and Aim
To investigate the value of changes in alpha-fetoprotein (AFP) levels for the prediction of radiologic response and survival outcomes in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) who received combined treatment of 3-dimensional conformal radiotherapy (3D-CRT) and transarterial chemoembolization (TACE).Methods
A database of 154 HCC patients with PVTT and elevated AFP levels (>20 ng/mL) treated with 3D-CRT and TACE as an initial treatment between August 2002 and August 2008 was retrospectively reviewed. AFP levels were determined 1 month after radiotherapy, and AFP response was defined as an AFP level reduction of >20% from the initial level. Radiologic response, overall survival (OS), and progression-free survival (PFS) rates were compared between AFP responders and non-responders. Propensity-score based matching analysis was performed to minimize the effect of potential confounding bias.Results
The median follow-up period was 11.1 months (range, 3.1–82.7 months). In the propensity-score matching cohort (92 pairs), a best radiologic response of CR or PR occurred in more AFP responders than AFP non-responders (41.3% vs. 10.9%, p < 0.001). OS and PFS were also longer in AFP responders than in non-responders (median OS 13.2 months vs. 5.6 months, p < 0.001; median PFS 8.7 months vs. 3.5 months, p < 0.001).Conclusions
AFP response is a significant predictive factor for radiologic response. Furthermore, AFP response is significant for OS and PFS outcomes. AFP evaluation after combined radiotherapy and TACE appears to be a useful predictor of clinical outcomes in HCC patients with PVTT. 相似文献13.
Sebastian Krug Michael Boch Hanna Daniel Wilhelm Nimphius Daniela Müller Patrick Michl Anja Rinke Thomas Matthias Gress 《PloS one》2015,10(12)
Background and Aim
Chemotherapy with streptozocin (STZ) in combination with 5-FU or doxorubicin (Dox) represents a standard of care for patients with metastatic pancreatic neuroendocrine neoplasms (pNEN). However, predictive markers for patient selection are still missing. The aim of this study was a retrospective evaluation of the clinicopathological characteristics of pNEN patients receiving STZ-based chemotherapies and to identify predictive and prognostic markers.Patients and Methods
We retrospectively analyzed 77 patients treated at our center between 1995 and 2013. The median overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier and Cox regression methods, respectively. Uni- and multivariate analyses were performed.Results
The median PFS (mPFS) in patients receiving STZ/5-FU/Dox was 16 months with a median OS (mOS) of 28 months. Objective response rate (ORR) and disease control rate (DCR) were 34% and 72%, respectively. Biochemical response and positive octreotide scintigraphy predicted objective response. Univariate analysis revealed Ki-67 > 10% and the absence of biochemical or objective response by imaging as independent risk factors for shorter PFS. Additionally, performance status (PS) and resection of the primary tumor were observed to influence mOS. Treatment was well tolerated with less than 10% grade 3 and 4 toxicities.Conclusions
STZ-based chemotherapy is an effective and well-tolerated treatment option in patients with well differentiated neuroendocrine neoplasms. Positive octreotide scintigraphy and biochemical response predict objective response. 相似文献14.
Wei Tian Wenping Ding Sungkyoung Kim Leizhen Zheng Li Zhang Xiaoping Li Jianchun Gu Lian Zhang Minggui Pan Siyu Chen 《PloS one》2013,8(7)
Objective
To evaluate the efficacy and safety profile of combining vandetanib with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).Methods
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ASCO Abstracts, ESMO Abstracts, Wanfang Database, CNKI were searched. Eligible studies were the randomized clinical trials (RCTs) that compared the efficacy and safety profile of adding vandetanib to chemotherapy with single chemotherapy in patients with advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities. All meta-analysis were performed using Review Manager 5.1. The fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p<0.1, or I2>50%), further analysis (subgroup analysis, sensitivity analysis or random-effect model) was performed to identify potential cause.Results
Results reported from 5 RCTs involving 2284 patients were included in the analysis. Compared to chemotherapy alone, the addition of vandetanib resulted in a significant longer PFS (HR 0.79 [0.72–0.87], p<0.00001) and a higher ORR (RR 1.75 [1.43–2.15], p<0.00001), but failed to show advantage on OS (HR 0.96 [0.87–1.06], p = 0.44).Conclusion
Vandetanib has activity in NSCLC. Identification of predictive biomarkers is warranted in future trials to select a subset of patients with advanced NSCLC who may benefit from vandetanib. 相似文献15.
Background
Constitutive activation of nuclear factor κB (NF-κB) is a hallmark of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Mutations in the A20 gene activate NF-κB, but the prognostic value of A20 mutations in ABC-DLBLC is unclear.Purpose
To investigate the prognostic value of A20 mutation in ABC-DLBCL patients.Methods
The somatic mutation of A20 was investigated in 68 de novo ABC-DLBCLs by PCR/sequencing. The Kaplan-Meier method was used to estimate median overall survival (OS) and progression-free survival (PFS).Results
The A20 mutation rate in ABC-DLBCL patients was 29.4%. Complete remission rates were 35% and 45.8% in patients with and without A20 mutations, respectively (P = 0.410). In patients with and without A20 mutations, the median OS was 24.0 and 30.6 months, respectively (P = 0.58), and the median PFS was 15 and 17.4 months, respectively (P = 0.52). None of the differences between the patient groups were significant.Conclusions
Our findings suggested that the A20 mutation is a frequent event in ABC-DLBCLs. However, there was no significant difference in PFS and OS in patients with or without A20 mutations. Further study is required to completely exclude A20 somatic mutation as a prognostic marker in the ABC subtype of DLBLC. 相似文献16.
Objectives
The indications for post-mastectomy radiotherapy (PMRT) with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.Methods
We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients).Results
The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS) (P = 0.010). Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005), but did not affect distant metastasis-free survival (DMFS) (P = 0.494), disease-free survival (DFS) (P = 0.215), and overall survival (OS) (P = 0.645). For patients without PMRT, the 5-year LRFS of low-risk patients (0–1 risk factor for locoregional recurrence) of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence) (80.9%, P < 0.001). PMRT improved LRFS (P = 0.001) and DFS (P = 0.027) in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.Conclusions
PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes. 相似文献17.
Xunlei Zhang Chunxiang Cao Qi Zhang Yi Chen Dongying Gu Yunzhu Shen Yongling Gong Jinfei Chen Cuiju Tang 《PloS one》2014,9(1)
Purpose
Oral fluoropyrimidine (S-1, capecitabine) has been considered as an important part of various regimens. We aimed to evaluate the efficacy and safety of S-1-based therapy versus capecitabine -based therapy in gastrointestinal cancers.Methods
Eligible studies were identified from Pubmed, EMBASE. Additionally, abstracts presented at American Society of Clinical Oncology (ASCO) conferences held between 2000 and 2013 were searched to identify relevant clinical trials. The outcome included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and advent events.Results
A total of 6 studies (4 RCTs and 2 retrospective analysis studies) containing 790 participants were included in this meta-analysis, including 401 patients in the S-1-based group and 389 patients in the capecitabine-based group. Results of our meta-analysis indicated that S-1-based and capecitabine-based regimens showed very similar efficacy in terms of PFS (HR 0.92, 95% CI 0.78–1.09, P = 0.360), OS (HR 1.01, 95% CI 0.84–1.21, P = 0.949), ORR (HR 1.04, 95% CI 0.87–1.25, P = 0.683) and DCR (HR 1.02, 95% CI 0.94–1.10, P = 0.639). There was also no significant difference in toxicity between regimens other than mild more hand–foot syndrome in capecitabine-based regimens.Conclusion
Both the S-1-based and capecitabine-based regimens are equally active and well tolerated, and have the potential of backbone chemotherapy regimen in further studies of gastrointestinal cancers. 相似文献18.
Yu-Mu Chen Chien-Hao Lai Huang-Chih Chang Tung-Ying Chao Chia-Cheng Tseng Wen-Feng Fang Chin-Chou Wang Yu-Hsiu Chung Yi-Hsi Wang Mao-Chang Su Shih-Feng Liu Kuo-Tung Huang Hung-Chen Chen Ya-Chun Chang Meng-Chih Lin 《PloS one》2016,11(2)
Background
Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases.Materials and Methods
This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users.Results
Fifty-seven patients (57/269, 21.2%) were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234). However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002). Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041). Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases.Conclusion
Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases. 相似文献19.
Background
Platinum-based standard chemotherapy improves survival of ovarian cancer (OC), but the five-year survival rate remains below 50%. Antiangiogenic agents (7.5 or 15 mg/kg Bevacizumab, Bev) plus to standard chemotherapy improve progression-free survival (PFS) not overall survival (OS) in completed randomized controlled trials (RCTs). The efficacy and safety of two doses of Bev + standard chemotherapy remain controversial.Methods
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane databases and ClinicalTrials.gov were searched. The outcomes of eligible RCTs included PFS, OS and toxicities. Hazard ratio (HR) and relative risk (RR) were used for the meta-analysis and were expressed with 95% confidence intervals (CIs).Results
Bev + chemotherapy improved PFS (HR, 0.82; 95% CI, 0.75 to 0.89; P = .000) and OS (HR, 0.87; 95% CI, 0.77 to 0.99; P = .026) in newly diagnosed OC (2 trials, 2776 patients), and PFS (HR, 0.48; 95% CI, 0.41 to 0.57; P = .000) in recurrent OC (2 trials, 845 patients). Bev + chemotherapy increased non-CNS bleeding (RR, 3.63; 95% CI, 1.81 to 7.29; P = .000), hypertension grade ≥ 2 (RR, 4.90; 95% CI, 3.83 to 6.25; P = .000), arterial thromboembolism (RR, 2.29; 95% CI, 1.33 to 3.94; P = .003), gastrointestinal perforation (RR, 2.90; 95% CI, 1.44 to 5.82; P = .003), and proteinuria grade ≥ 3 (RR, 6.63; 95% CI 3.17 to 13.88; P = .000). No difference was observed between the two Bev doses in PFS (HR, 1.04; 95% CI, 0.88 to 1.24) or OS (HR, 1.15, 95% CI, 0.88 to 1.50), but 15 mg/kg Bev increased toxicities.Conclusion
Bev + standard chemotherapy delayed progression for newly diagnosed and recurrent OC, and improved survival for newly diagnosed OC. The 7.5 mg/kg dose appeared to be optimal for newly diagnosed OC patients with high risk for progression. 相似文献20.
Lin Quan Tang Dong Peng Hu Qiu Yan Chen Lu Zhang Xiao Ping Lai Yun He Yun-Xiu-Xiu Xu Shi-Hua Wen Yu-Tuan Peng Wen-Hui Chen Shan-Shan Guo Li-Ting Liu Chao-Nan Qian Xiang Guo Mu-Sheng Zeng Hai-Qiang Mai 《PloS one》2015,10(4)
