The Efficacy of Combining Antiangiogenic Agents with Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer Who Failed First-Line Chemotherapy: A Systematic Review and Meta-Analysis

Background

The clinical outcomes of patients with NSCLC who progressed after first-line treatments remain poor. The purpose of this study was to assess the advantage of antiangiogenic therapy plus standard treatment versus standard treatment alone for this population of patients.

Methods

We conducted a rigorous search using electronic databases for eligible studies reporting antiangiogenic therapy combined with standard second-line chemotherapy versus standard second-line treatment for patient who progressed after front-line treatment. Pooled risk ratio and 95% confidence intervals were calculated using proper statistical method. Predefined subgroup analyses were conducted to identify the potential proper patients.

Results

Thirteen phase II/III RCTs which involved a total of 8358 participants were included. Overall, there was significant improvement in OS (HR 0.94, 95%CI: 0.89-0.99, p=0.03), PFS (HR 0.80, 95%CI: 0.76-0.84, p<0.00001), ORR (RR 1.75, 95%CI: 1.55-1.98, p<0.00001) and DCR (RR 1.23, 95%CI: 1.18-1.28, p<0.00001) in the group with antiangiogenic therapy plus standard treatment versus the group with standard treatment alone. Subgroup analysis showed that OS benefit was presented only in patients treated with docetaxel plus antiangiogenic agents (HR 0.92, 95%CI: 0.86-0.99, p=0.02) and patients with non-squamous NSCLC (HR for OS 0.92, 95%CI: 0.86-0.99, p=0.02).

Conclusions

This study revealed that the addition of antiangiogenic agents to the standard treatments could provide clinical benefit to NSCLC patients who failed their first-line therapy. Furthermore, proper selection of the combined standard cytotoxic agent, as well as the patient population by tumor histology, is warranted for future studies and clinical application of antiangiogenic therapy.     

Combined EGFR and VEGFR versus Single EGFR Signaling Pathways Inhibition Therapy for NSCLC: A Systematic Review and Meta-Analysis

Background

Lung cancer is a heterogeneous disease with multiple signaling pathways influencing tumor cell survival and proliferation, and it is likely that blocking only one of these pathways allows others to act as salvage or escape mechanisms for cancer cells. Whether combined inhibition therapy has greater anti-tumor activity than single inhibition therapy is a matter of debate. Hence, a meta-analysis comparing therapy inhibiting both VEGFR and EGFR signaling pathways with that inhibiting EGFR signaling pathway alone was performed.

Methodology and Principal Findings

We searched PubMed, EMBASE database and the proceedings of major conferences for relevant clinical trials. Outcomes analyzed were objective tumor response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Besides, subgroup analyses were performed to investigate whether the combined inhibition therapy is best performed using combination of selective agents or a single agent with multiple targets.Six trials recruiting 3,302 patients were included in the analysis. Combined inhibition therapy was associated with a 3% improvement in OS as compared with single-targeted therapy, but this difference was not statistically significant (HR, 0.97; 95% CI, 0.89–1.05; P = 0.472). Patients receiving combined inhibition therapy had significant longer PFS than the group with single-targeted therapy (HR, 0.80; 95% CI, 0.67–0.95; P = 0.011). There was no difference in the ORR between the groups (OR, 1.44; 95% CI, 0.95–2.18; P = 0.085). Subgroup analysis revealed that combined inhibition therapy using combination regimens was associated with statistically significant improvement in both ORR and PFS. Toxicity was greater in combined inhibition therapy.

Conclusions

There is no evidence to support the use of combined inhibition therapy in unselected patients with advanced NSCLC. However, given the significant advantage in ORR and PFS, combined inhibition therapy using combination regimens may be considered for further evaluation in subsets of patients who may benefit from this treatment.     

S-1-Based Chemotherapy versus Capecitabine-Based Chemotherapy as First-Line Treatment for Advanced Gastric Carcinoma: A Meta-Analysis

Background

Although both oral fluoropyrimidines were reported effective and safe, doubts exist about whether S-1 or capecitabine is more advantageous in advanced gastric carcinoma (AGC). Herein, we performed a meta-analysis to comprehensively compare the efficacy and safety of S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for AGC.

Methods

PubMed/Medline, EmBase, Cochrane library, and China National Knowledge Infrastructure databases were searched for articles comparing S-1-based chemotherapy to capecitabine-based chemotherapy for AGC. Primary outcomes were overall response rate (ORR), time to progression (TTP), overall survival (OS), progression-free probability, and survival probability. Secondary outcomes were toxicities. Fixed-effects model were used and all the results were confirmed by random-effects model.

Results

Five randomized controlled trials and five cohort studies with 821 patients were included. We found equivalent ORR (38.3% vs. 39.1%, odds ratio [OR] 0.92, 95% confidence interval [CI] 0.69-1.24, P = 0.59), TTP (harzad ratio [HR] 0.98, 95% CI 0.82-1.16, P = 0.79), OS (HR 0.99, 95% CI 0.87-1.13, P = 0.91), progression-free probability (3-month OR 1.02, 95% CI 0.62-1.68, P = 0.94; 6-month OR 1.34, 95% CI 0.88-2.04, P = 0.18) and survival probability (0.5-year OR 0.90, 95% CI 0.61-1.31, P =0.57; 1-year OR 0.97, 95% CI 0.70- 1.33, P = 0.84; 2-year OR 1.15, 95% CI 0.61-2.17, P = 0.66). Equivalent grade 3 to 4 hematological and non-hematological toxicities were found except hand-foot syndrome was less prominent in S-1-based chemotherapy (0.3% vs. 5.9%, OR 0.19, 95% CI 0.06-0.56, P = 0.003). There’re no significant heterogeneity and publication bias. Cumulative analysis found stable time-dependent trend. Consistent results stratified by study design, age, regimen, cycle, country were observed.

Conclusion

S-1-based chemotherapy was associated with non-inferior antitumor efficacy and better safety profile, compared with capecitabine-based therapy. We recommended S-1 and capecitabine can be used interchangeably for AGC, at least in Asia.     

贝伐珠单抗联合化疗治疗晚期结直肠癌的临床疗效

目的:探讨晚期结直肠癌采用贝伐珠单抗联合化疗的临床疗效,为临床治疗提供参考。方法:按照随机数字表法将2010年2月~2013年2月我院收治的50例晚期结直肠癌患者分为两组,观察组采用贝伐珠单抗联合奥沙利铂,卡培他滨化疗,对照组单用奥沙利铂,卡培他滨进行化疗,比较两组的临床疗效、血清肿瘤标志物浓度变化及不良反应。结果:化疗4个周期后观察组有效率为56.00%高于对照组的24.00%,差异有统计学意义(P0.01),观察组疾病控制率为84.00%高于对照组的60.00%,差异有统计学意义(P0.05);观察组治疗后的CEA、CA242、CA19-9浓度均低于对照组,差异有统计学意义(P0.01);化疗后两组不良反应主要有恶心、呕吐、食欲减低等胃肠道反应,乏力,肝功能损害,骨髓抑制,脱发,贫血以及中性粒细胞下降等,其中观察组乏力,肝功能损害发生率低于对照组,差异有统计学意义(P0.05),其余不良反应两组差异无统计学意义(P0.05)。结论:结直肠癌采用贝伐珠单抗联合化疗治疗具有近期疗效好,安全性高等特点,临床有重要参考价值。     

Treatment Efficacy for Non-Cardiovascular Chest Pain: A Systematic Review and Meta-Analysis

Background

Non-cardiovascular chest pain (NCCP) leads to impaired quality of life and is associated with a high disease burden. Upon ruling out cardiovascular disease, only vague recommendations exist for further treatment.

Objectives

To summarize treatment efficacy for patients presenting with NCCP.

Methods

Systematic review and meta-analysis. In July 2013, Medline, Web of Knowledge, Embase, EBSCOhost, Cochrane Reviews and Trials, and Scopus were searched. Hand and bibliography searches were also conducted. Randomized controlled trials (RCTs) evaluating non-surgical treatments in patients with NCCP were included. Exclusion criteria were poor study quality and small sample size (<10 patients per group).

Results

Thirty eligible RCT’s were included. Most studies assessed PPI efficacy for gastroesophageal reflux disorders (GERD, n = 10). Two RCTs included musculoskeletal chest pain, seven psychotropic drugs, and eleven various psychological interventions. Study quality was high in five RCTs and acceptable in 25. PPI treatment in patients with GERD (5 RCTs, 192 patients) was more effective than placebo [pooled OR 11.7 (95% CI 5.5 to 25.0, heterogeneity I² = 6.1%)]. The pooled OR in GERD negative patients (4 RCTs, 156 patients) was 0.8 (95% CI 0.2 to 2.8, heterogeneity I² = 50.4%). In musculoskeletal NCCP (2 RCTs, 229 patients) manual therapy was more effective than usual care but not than home exercise [pooled mean difference 0.5 (95% CI −0.3 to 1.3, heterogeneity I² = 46.2%)]. The findings for cognitive behavioral treatment, serotonin reuptake inhibitors, tricyclic antidepressants were mixed. Most evidence was available for cognitive behavioral treatment interventions.

Limitations

Only a small number of studies were available.

Conclusions

Timely diagnostic evaluation and treatment of the disease underlying NCCP is important. For patients with suspected GERD, high-dose treatment with PPI is effective. Only limited evidence was available for most prevalent diseases manifesting with chest pain. In patients with idiopathic NCCP, treatments based on cognitive behavioral principles might be considered.     

局部进展期胃癌术前动静脉结合化疗的疗效观察

目的:局部进展期胃癌,即使没有出现远处转移或腹膜种植,预后也极不理想.我们对局部进展期胃癌患者进行术前mECF方案的动静脉结合化疗,以评价其治疗疗效.方法:选取自2009年1月至2011年6月间我院局部进展期胃癌Ⅱ-ⅢC期患者38例,均由影像学确定淋巴结高度可疑转移或浸润、包绕主要血管结构,且没有发现远处转移或腹膜种植,进行2个周期的术前动静脉结合化疗后,行手术治疗.记录化疗毒性反应、临床、病理缓解率、手术并发症发生率和病死率以及1年无病生存率.结果:化疗毒性反应低,3级反应不超过10％,仅有1例出现4级反应,表现为腹泻、恶心和呕吐.38例患者中临床CR有6例,占15.8％,PR17例,占44.7％,NC13例(34.2％),PD2例(5.3％),RR为60.5％(23/38).全部患者均施行了手术,37例患者进行了根治性手术,R0切除率为97％.病理缓解率为5例完全缓解(13.2％),21例部分缓解(55.3％),8例轻微缓解(21.1％),4例未缓解(10.5％).手术并发症发生率为7.9％,无治疗相关死亡发生.1年无病生存率为81.6％.结论:局部进展期胃癌患者术前进行mECF方案的动静脉化疗毒性反应低,疗效理想,之后行手术完整切除后临床效果突出,是理想的治疗方法.     

XRCC3 Thr241Met Polymorphism and Clinical Outcomes of NSCLC Patients Receiving Platinum-Based Chemotherapy: A Systematic Review and Meta-Analysis

Introduction

X-ray repair cross-complementing protein 3 (XRCC3) is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy.

Methods

A systematic review and meta-analysis was performed to evaluate the predictive value of XRCC3 Thr241Met polymorphism on clinical outcomes of advanced NSCLC receiving platinum-based chemotherapy. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were analyzed.

Results

A number of 11 eligible studies were identified according to the inclusion criteria. Carriers of the variant XRCC3 241Met allele were significantly associated with good response to platinum-based chemotherapy (ThrMet/MetMet vs. ThrThr: OR  = 1.509, 95% CI: 1.099–2.072, P_{heterogeneity}  = 0.618). The XRCC3 Thr241Met polymorphism was not associated with OS (MetMet vs. ThrThr, HR  = 0.939, 95% CI:0.651–1.356, P_{heterogeneity}  = 0.112) or PFS (MetMet vs. ThrThr, HR  = 0.960, 95% CI: 0.539–1.710, P_{heterogeneity}  = 0.198). Additionally, no evidence of publication bias was observed.

Conclusions

This systematic review and meta-analysis shows that carriers of the XRCC3 241Met allele are associated with good response to platinum-based chemotherapy in advanced NSCLC, while the XRCC3 Thr241Met polymorphism is not associated with OS or PFS.     

Safety and Efficacy of Co-Trimoxazole for Treatment and Prevention of Plasmodium falciparum Malaria: A Systematic Review

Introduction

Cotrimoxazole (CTX) has been used for half a century. It is inexpensive hence the reason for its almost universal availability and wide clinical spectrum of use. In the last decade, CTX was used for prophylaxis of opportunistic infections in HIV infected people. It also had an impact on the malaria risk in this specific group.

Objective

We performed a systematic review to explore the efficacy and safety of CTX used for P.falciparum malaria treatment and prophylaxis.

Result

CTX is safe and efficacious against malaria. Up to 75% of the safety concerns relate to skin reactions and this increases in HIV/AIDs patients. In different study areas, in HIV negative individuals, CTX used as malaria treatment cleared 56%–97% of the malaria infections, reduced fever and improved anaemia. CTX prophylaxis reduces the incidence of clinical malaria in HIV-1 infected individuals from 46%–97%. In HIV negative non pregnant participants, CTX prophylaxis had 39.5%–99.5% protective efficacy against clinical malaria. The lowest figures were observed in zones of high sulfadoxine-pyrimethamine resistance. There were no data reported on CTX prophylaxis in HIV negative pregnant women.

Conclusion

CTX is safe and still efficacious for the treatment of P.falciparum malaria in non-pregnant adults and children irrespective of HIV status and antifolate resistance profiles. There is need to explore its effect in pregnant women, irrespective of HIV status. CTX prophylaxis in HIV infected individuals protects against malaria and CTX may have a role for malaria prophylaxis in specific HIV negative target groups.     

Efficacy of 5-Nitroimidazoles for the Treatment of Giardiasis: A Systematic Review of Randomized Controlled Trials

Background

Giardiasis is one of the most common causes of diarrheal disease worldwide and 5-nitroimidazoles (5-NI) are the most commonly prescribed drugs for the treatment of giardiasis. We evaluated the efficacy of 5-nitroimidazoles (5-NI) in the treatment of giardiasis in a systematic review of randomized controlled trials (RCTs).

Methodology/Principal Findings

We conducted a comprehensive literature search in PubMed-Medline, Scopus, Web of Science and Cochrane Library for RCTs evaluating the efficacy of 5-NI vs. control (placebo or active treatment) on parasitological cure in patients with parasitologically-demonstrated giardiasis. The search was performed in May 2013 with no language restriction by two authors independently. The efficacy outcome was parasitological cure, and harmful outcomes were abdominal pain, bitter or metallic taste, and headache. We included 30 RCTs (n = 3,930). There was a significant and slightly higher response rate with 5-NI in giardiasis treatment (RR 1.06, 95%CI 1.02–1.11, p = 0.005). There was high heterogeneity among studies (I² = 72%). The response rates for metronidazole, tinidazole and secnidazole were similar (RR 1.05, 95%CI 1.01–1.09, p = 0.01; RR 1.32 95%CI 1.10–1.59, p = 0.003; and RR 1.18 95%CI 0.93–1.449, p = 0.18, respectively). On subgroup analyses, the response rates did not vary substantially and high heterogeneity persisted (I² = 57%–80%). Harmful outcomes were uncommon, and 5-NIs were associated with lower risk of abdominal pain, and higher risk of both bitter or metallic taste and headache.

Conclusions

Studies investigating the efficacy of 5-NI in giardiasis treatment are highly heterogeneous. 5-NIs have a slightly better efficacy and worse profile for mild harmful outcomes in the treatment of giardiasis in comparison to controls. Larger high quality RCTs are needed to further assess efficacy and safety profiles of 5-NI.     

Clinical Efficacy of Including Capecitabine in Neoadjuvant Chemotherapy for Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients.

Methods

The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1.

Results

Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87–1.40, p = 0.43), pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83–1.18, p = 0.90), overall response rate (ORR; RR = 1.00, 95% CI 0.94–1.07, p = 0.93), or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93–1.04, p = 0.49).

Conclusions

Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.     

Dihydroartemisinin-Piperaquine vs. Artemether-Lumefantrine for First-Line Treatment of Uncomplicated Malaria in African Children: A Cost-Effectiveness Analysis

Background

Recent multi-centre trials showed that dihydroartemisinin-piperaquine (DP) was as efficacious and safe as artemether-lumefantrine (AL) for treatment of young children with uncomplicated P. falciparum malaria across diverse transmission settings in Africa. Longitudinal follow-up of patients in these trials supported previous findings that DP had a longer post-treatment prophylactic effect than AL, reducing the risk of reinfection and conferring additional health benefits to patients, particularly in areas with moderate to high malaria transmission.

Methods

We developed a Markov model to assess the cost-effectiveness of DP versus AL for first-line treatment of uncomplicated malaria in young children from the provider perspective, taking into consideration the post-treatment prophylactic effects of the drugs as reported by a recent multi-centre trial in Africa and using the maximum manufacturer drug prices for artemisinin-based combination therapies set by the Global Fund in 2013. We estimated the price per course of treatment threshold above which DP would cease to be a cost-saving alternative to AL as a first-line antimalarial drug.

Results

First-line treatment with DP compared to AL averted 0.03 DALYs (95% CI: 0.006–0.07) and 0.001 deaths (95% CI: 0.00–0.002) and saved $0.96 (95% CI: 0.33–2.46) per child over one year. The results of the threshold analysis showed that DP remained cost-saving over AL for any DP cost below $1.23 per course of treatment.

Conclusions

DP is superior to AL from both the clinical and economic perspectives for treatment of uncomplicated P. falciparum malaria in young children. A paediatric dispersible formulation of DP is under development and should facilitate a targeted deployment of this antimalarial drug. The use of DP as first-line antimalarial drug in paediatric malaria patients in moderate to high transmission areas of Africa merits serious consideration by health policymakers.     

吡喃阿霉素联合化疗癌症的有效性与安全性

目的:探讨以吡喃阿霉素(THP)为主的联合化疗方案治疗恶性肿瘤的疗效与安全性。方法:以THP与其他2～3种抗癌药物联合治疗84例各类恶性肿。统计近期疗效,观察THP所致的心脏毒性发生率和其他并发症。结果:完全缓解14例,部分缓解30例、稳定36例,无效5例,总有效率52.38%。67例出现各类不良反应126例次,但程度均较轻。结论:以THP为主的联合化疗方案治疗恶性肿瘤疗效明显,毒性反应程度较轻。     

吡喃阿霉素联合化疗癌症的有效性与安全性

目的：探讨以吡喃阿霉素（THP）为主的联合化疗方案治疗恶性肿瘤的疗效与安全性。方法：以THP与其他2～3种抗癌药物联合治疗84例各类恶性肿。统计近期疗效,观察THP所致的心脏毒性发生率和其他并发症。结果：完全缓解14例,部分缓解30例、稳定36例,无效5例,总有效率52.38%。67例出现各类不良反应126例次,但程度均较轻。结论：以THP为主的联合化疗方案治疗恶性肿瘤疗效明显,毒性反应程度较轻。     

Efficacy and Safety of Bevacizumab for the Treatment of Advanced Hepatocellular Carcinoma: A Systematic Review of Phase II Trials

Background

Hepatocellular carcinoma (HCC) is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC.

Methods

PubMed, the Cochrane Library, and Google Scholar were searched using the terms “bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable)”. Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS), tumor response, and toxicities.

Results

A total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial) or in combination with erlotinib (n = 4 trials), capecitabine (n = 1 trial), capecitabine+oxaliplatin (n = 1 trial), or gemcitabine+oxaliplatin (n = 1 trial). Most trials (five of eight) reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%), fatigue (12%), hypertension (10%), diarrhea (8%), and neutropenia (5%). Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12), typically due to esophageal varices.

Conclusions

Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently approved treatment for unresectable HCC. Phase III trials are warranted to comprehensively examine the efficacy and safety of bevacizumab for treatment of advanced HCC.     

The Efficacy and Safety of Leflunomide for the Treatment of Lupus Nephritis in Chinese Patients: Systematic Review and Meta-Analysis

Objective

To evaluate the clinical efficacy and safety of leflunomide as a new immunosuppressive medicine in lupus nephritis (LN) through a meta-analysis.

Methods

A systematic review evaluating the efficacy and safety of leflunomide compared with cyclophosphamide in adult patients with LN was performed. Data from relevant randomized controlled trials (RCTs) performed before December 2014 was collected from several databases (PubMed, Embase, Cochrane Library, CNKI and CBM). No language restrictions were applied. Efficacy outcomes included overall remission, SLE Disease Activity Index (SLEDAI) score, 24-hour proteinuria and serum creatinine. Safety data were analyzed. The effects of treatment on these outcomes were summarized as relative risks (RRs) with 95% confidence intervals (CIs) and mean differences were pooled using a fixed or random effects model.

Results

Eleven RCTs with Jadad score of 3 or greater were identified and included a total of 254 patients. Cyclophosphamide was served as the control drug in all trials. The SLEDAI score, urine protein level and serum creatinine decreased significantly following leflunomide treatment (P<0.05). Leflunomide was superior to cyclophosphamide in achieving complete and total remission, but no difference in SLEDAI score was found between these two treatments (P>0.05). Additionally, patients receiving leflunomide treatment showed favorable renal function profiles, especially regarding the 24-hour proteinuria (mean difference: -0.58, 95%CI: -0.78~-0.37, P<0.01) and serum creatinine (mean difference: -0.20, 95%CI: -0.39~-0.01, P<0.05). In the safety comparison, leflunomide was safer than cyclophosphamide regarding adverse drug reactions (ADRs), including liver damage (RR = 0.53, 95%CI: 0.33~0.87, P<0.05), alopecia (RR = 0.38, 95%CI: 0.17~0.85, P<0.05), leukopenia (RR = 0.25, 95%CI: 0.08~0.77, P<0.05) and infection (RR = 0.54, 95%CI: 0.32~0.92, P<0.05), without increased risk of gastrointestinal reaction, rash or herpes zoster infection.

Conclusions

Leflunomide is a promising therapy for LN treatment, primarily because of the comparable efficacy and favorable safety profile determined by this meta-analysis of RCTs. Larger RCTs with longer duration of observation are necessary to provide strong evidence of the efficacy and safety of leflunomide in LN patients.     

The Effect of Tuberculosis Treatment at Combination Antiretroviral Therapy Initiation on Subsequent Mortality: A Systematic Review and Meta-Analysis

Objective

We aimed to perform a systematic review and meta-analysis examining the impact of TB treatment at the time of combination antiretroviral therapy (cART) initiation on subsequent mortality.

Methods

We searched PubMed, EMBASE, and selected conference proceedings for studies that report adult mortality on cART, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used to examine the influence of study and population characteristics.

Results

22 eligible cohort studies reported data on 98,350 (range 74-15,225) adults, of whom 14,779 (15%) were receiving TB treatment at cART initiation. Studies of those receiving vs. not receiving TB treatment had an average mortality relative risk of 1.10 (95% confidence interval 0.87-1.40) at 1-3 months (based upon 8 estimates), 1.15 (0.94-1.41) at 6-12 months (11 estimates), and 1.33 (1.02-1.75) at 18-98 months (10 estimates) following cART initiation. However, there was a wide range of estimates and those at later time points were markedly heterogeneous. Meta-regression identified factors associated with elevated average risk estimates: lower median baseline CD4 counts and adjustment for baseline hemoglobin at 1-3 months; longer length of follow-up and women-only studies at 6-12 months; and not adjusting for BMI/weight at 18-98 months.

Conclusions

Patients receiving TB treatment at cART initiation did not have a statistically significant estimated increase in short-term risk of all-cause mortality as compared to those not receiving TB treatment. TB treatment was significantly associated with increased mortality after about a year of cART, suggesting that patients with concurrent TB treatment at cART initiation may benefit from continued support after TB treatment completion.     

MET Gene Amplification and MET Receptor Activation Are Not Sufficient to Predict Efficacy of Combined MET and EGFR Inhibitors in EGFR TKI-Resistant NSCLC Cells

Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer. Human non small cell lung cancers (NSCLC) with activating mutations in the EGFR gene frequently experience significant tumor regression when treated with EGFR tyrosine kinase inhibitors (TKIs), although acquired resistance invariably develops. Resistance to TKI treatments has been associated to secondary mutations in the EGFR gene or to activation of additional bypass signaling pathways including the ones mediated by receptor tyrosine kinases, Fas receptor and NF-kB. In more than 30–40% of cases, however, the mechanisms underpinning drug-resistance are still unknown. The establishment of cellular and mouse models can facilitate the unveiling of mechanisms leading to drug-resistance and the development or validation of novel therapeutic strategies aimed at overcoming resistance and enhancing outcomes in NSCLC patients. Here we describe the establishment and characterization of EGFR TKI-resistant NSCLC cell lines and a pilot study on the effects of a combined MET and EGFR inhibitors treatment. The characterization of the erlotinib-resistant cell lines confirmed the association of EGFR TKI resistance with loss of EGFR gene amplification and/or AXL overexpression and/or MET gene amplification and MET receptor activation. These cellular models can be instrumental to further investigate the signaling pathways associated to EGFR TKI-resistance. Finally the drugs combination pilot study shows that MET gene amplification and MET receptor activation are not sufficient to predict a positive response of NSCLC cells to a cocktail of MET and EGFR inhibitors and highlights the importance of identifying more reliable biomarkers to predict the efficacy of treatments in NSCLC patients resistant to EGFR TKI.     

金龙胶囊联合化疗治疗晚期非小细胞肺癌临床疗效观察

目的:观察金龙胶囊联合化疗与单纯化疗对晚期肺小细胞癌患者的疗效、生活质量等因素的影响。方法:将99例患有晚期非小细胞肺癌患者随机分为两组:治疗组,在NP化疗方案基础上加服金龙胶囊治疗;对照组,单纯接受NP方案化疗。对99例患者追踪2个月,观察并比较患者的疗效、体质量、生活质量、毒副反应等方面的差异。结果:在NP化疗方案基础上加服金龙胶囊治疗在患者疗效评价方面与单纯NP方案化疗相比不具有统计学差异(P>0.05);在提高患者体质量、改善患者临床症状和生活质量等方面均优于单纯NP方案化疗(P<0.05);在化疗所引发的白细胞、血红蛋白和血小板降低等部分毒副反应发生率方面低于单纯NP方案化疗组(P<0.05)。结论:金龙胶囊联合NP化疗治疗晚期非小细胞肺癌不仅可以起到化疗增效的作用,而且能够明显提高患者生活质量,有效的改善临床症候,降低化疗引发的毒副反应,这一联合治疗方案可以在临床治疗中广泛推广。