迪利单抗对肺癌患者嗜酸性气道炎症的研究

目的 探讨信迪利单抗对肺癌患者嗜酸性气道炎症的影响。方法 选取2019年4月—2020年4月于徐州医科大学附属宿迁医院就诊的60例IV期非鳞非小细胞肺癌患者,随机分为对照组(单纯化疗组)和试验组(信迪利单抗联合化疗组);对照组给予培美曲塞500 mg/m2联合顺铂75 mg/m2静脉注射;试验组在对照组治疗方案基础上联合免疫检查点抑制剂信迪利单抗200 mg静脉注射,均21天为1个周期。6个周期治疗后检测两组患者呼出气一氧化氮(Fractional exhaled nitric oxide,FeNO)、外周血嗜酸性粒细胞计数、肺功能及动脉血气;分析信迪利单抗治疗组严重不良事件(SAE)及免疫相关性肺炎(CIP)的发生率。结果 ⑴试验组在第2、4、6周期治疗后FeNO水平、外周血嗜酸性粒细胞计数相较于基线水平出现升高趋势,但差异无统计学意义(PFeNO=0.536; PEos=0.762)。⑵两组患者经6个周期治疗后,第1秒用力呼吸容积(FEV1)、用力肺活量(FVC)、FEV1/FVC、一氧化碳弥散量占预计值百分比(DLco%)较治疗前均无明显变化(PFEV1=0.615; PFVC=0.473; PFEV1/FVC=0.637; PDLco%=0.598);动脉血气分析中PH、PaO2、PaCO2水平较治疗前均无明显变化(PPH=0.457; PPaCO2=0.242; PPaO2=0.631)。⑶试验组免疫相关SAE发生率和CIP的发生率均为0。结论 6周期治疗后信迪利单抗对肺癌患者的嗜酸性气道炎症、肺功能、动脉血气分析无明显影响,未出现免疫相关SAE及CIP。     

A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer

Current pemetrexed/platinum chemotherapy does not produce a satisfactory therapeutic response in advanced lung cancer patients. The aim of this study was to determine whether the administration of gefitinib, a tyrosine kinase inhibitor (TKI), intercalated with pemetrexed/platinum could improve the efficacy in chemotherapy-naïve patients with advanced non-squamous NSCLC without subsequent gefitinib maintenance therapy. Treatment-naïve patients with stage IIIB or IV NSCLC were randomly assigned to receive pemetrexed (500 mg/m² d1) and either cisplatin (75 mg/m² d1) or carboplatin (AUC = 5 d1) plus gefitinib (250 mg/d on days 3 to 16 of a 3-week cycle) (PC-G) or pemetrexed–platinum (PC) alone. Randomization was stratified according to the tobacco smoking status and EGFR mutational status of the patients. The primary endpoint was the non-progression rate (NPR) at 12 weeks. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and biosafety. The NPR at 12 weeks was 84.5% for the PC-G treatment arm and 83.1% for the PC treatment arm (P = 0.87). Median PFS was 7.9 months for the PC-G arm and 7.0 months for the PC arm (P = 0.57). The ORR was 50.0% for the PC-G arm and 47.4% for the PC arm (P = 0.78). Median survival was 25.4 mo for the PC-G arm and 20.8 mo for the PC arm (P = 0.54). The incidence of adverse events was similar between the two treatment arms, except for a higher incidence of skin rash with PC-G. Predefined subgroup analyses demonstrated that PC-G significantly increased the PFS compared with the PC regimen in patients with EGFR mutations (P = 0.017). Although gefitinib intercalated with pemetrexed/platinum chemotherapy did not improve the NPR at 12 weeks compared with chemotherapy, an improvement in the PFS for the intercalated treatment arm was seen in the subgroup of patients with EGFR mutations.     

培美曲塞联合卡铂治疗老年晚期非鳞非小细胞肺癌临床疗效分析

目的评价培美曲塞联合卡铂治疗老年晚期非鳞非小细胞肺癌的临床疗效及毒副作用。方法92例晚期非鳞非小细胞肺癌老年患者,其中培美曲塞联合卡铂（Pc组）治疗42例,吉西他滨联合卡铂（GC组）治疗50例。结果Pc组和GC组疾病控制率（DCR）为73．8％及70．2％（P〉0．05）。PC组毒副反应发生率小于GC组。结论培美曲塞联合卡铂治疗老年晚期非鳞非小细胞肺癌的疗效与吉西他滨联合卡铂的疗效相当,但副作用明显减少,患者耐受性更好。     

Non-squamous cell carcinoma diseases of the larynx: clinical and imaging findings

IntroductionSquamous cell carcinoma is the most common laryngeal neoplasm and accounts for approximately 95% of all malignant neoplams of the larynx. However, various benign and malignant tumors and inflammatory diseases may affect the larynx.ObjectiveThe purpose of this study is to analyze the clinical and imaging findings of non-squamous cell neoplasms and inflammatory diseases of the larynx.MethodsThis retrospective study was conducted in 18 patients who were diagnosed with non-squamous cell carcinoma lesions of larynx at our institution between 2007-2017. Clinical symptoms, examination findings, imaging characteristics, histopathologic diagnosis and treatment modalities were analyzed.ResultsThere were 9 malignant lesions (2 chondrosarcoma, 1 neuroendocrine tumor-atipical carcinoid, 1 Natural Killer/T-cell lymphoma, 1 diffuse large B-cell lymphoma, 3 plasmocytoma-multiple myeloma involvement, 1 adenocarcinoma metastasis), 3 benign neoplasms (chondroma, paraganglioma, lipoma), 2 tumor-like lesions (Brown tumor and inflammatory myofibroblastic tumor), 3 inflammatory lesions (Wegener granulomatosis, Behçet's disease and tuberculosis involvements), and 1 vascular malformation. The most common presenting symptom was hoarseness (66.6%). Paraganglioma was seen as hypervascular lesion on computed tomography and magnetic resonance imaging and showed intense tracer uptake on 68Gallium-DOTA-peptide PET/CT. Chondroid matrix calcifications were detected in chondroma and chondrosarcoma-grade 1. In patients with vascular malformation and lipoma, the typical imaging findings made it possible to diagnose.ConclusionImaging studies may provide clues for diagnosis of non-squamous cell laryngeal lesions. Clinical and imaging findings and previous clinical history should be evaluated together in clinical management of laryngeal lesions.     

三维适形放疗联合培美曲塞治疗非鳞癌局部晚期肺癌的近期疗效

目的观察三维适形放疗联合培美曲塞治疗非鳞癌局部晚期肺癌的近期疗效及毒性反应。方法将我院收治的非鳞癌局部晚期肺癌患者56例随机分为对照组(n=28)与观察组(n=28),所有患者均行三维适形放疗,观察组患者在此基础上加用培美曲塞静脉滴注。结果观察组患者治疗后有效率为60.71%,控制率为82.14%,均明显高于对照组(分别为35.71%和59.52%(P<0.05);两组患者毒副反应发生率比较无显著性差异(P>0.05)。结论三维适形放疗联合培美曲塞治疗非鳞癌局部晚期肺癌疗效显著,且未明显增加毒副反应,值得临床推广和应用。     

PEM/DDP对晚期非鳞肺癌患者心理状况及睡眠质量的影响及参麦注射液的作用

目的探讨PEM/DDP对晚期非鳞肺癌患者心理状况及睡眠质量的影响及参麦注射液的作用。方法选取2009年7月～2017年12月收治的晚期(Ⅲ～Ⅳ期)非鳞肺癌患者60例,按照治疗方法的不同随机分为研究组和对照组两组,各30例,两组患者在治疗后均接受常规生物学指标检查。研究组采用PEM/DDP化疗联合参麦注射液进行治疗,每次化疗第0～7天接受参麦注射液静脉滴注;对照组单独使用PEM/DDP化疗,每3周重复化疗,观察两组患者的治疗方法对心理状况以及睡眠质量的影响及对两组患者的不良反应。结果研究组患者的心理状况、睡眠质量、生活质量等评分显著优于对照组(P0.05)。对照组焦虑自评量表(SAS)以及抑郁自评量表(SDS)评分分别为(35.3±3.2)分、(35.3±3.2)分,研究组SAS以及SDS评分分别为(23.2±3.1)分、(23.2±3.1)分;对照组和研究组在治疗8周后PSQI评分分别为(8.2±1.3)分、(6.9±1.1)分。研究组不良反应发生率显著低于对照组(P0.05)。结论 PEM/DDP化疗联合参麦注射液治疗晚期非鳞肺癌患者的临床疗效显著,对患者的心理状况、睡眠质量有改善作用,可提高晚期非鳞肺癌患者的生活质量,值得推广与应用。     

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies

Objectives: This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5?mg/min?mL (PCb5) or 6?mg/min?mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer.

Methods: All patients received pemetrexed 500?mg/m² every 21 days with either of two carboplatin doses for up to 4–6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized.

Results: A total of 486 patients mainly from the US, Europe, and East Asia were included in the analysis; 22% (n?=?105) received PCb5 in one trial and 78% (n?=?381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 vs PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses.

Conclusions: Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient’s characteristics and trial designs, the results show that the PCb5 regimen was generally associated with a better safety profile than PCb6 across three statistical approaches, with no apparent impact on survival outcomes.     

Safety profiles of first-line therapies for metastatic non-squamous non-small-cell lung cancer

ABSTRACT

Introduction: Lung cancer still represents the leading cause of death for cancer. About the 70% of diagnosis are in advanced-stage. Non-small-cell lung cancer (NSCLC) represents the 85% of all diagnosed lung cancers and non-squamous histology represents the 40% of all NSCLC. First-line therapies increase survival, control symptoms and improve quality of life, compared with best supportive care. It is crucial to choose a treatment with a low impact on patient’s life considering the related toxicities.

Areas covered: Adverse events (AEs) of first-line therapies for non-squamous NSCLC are here reviewed and discussed, from evidences in clinical trials conducting to drugs approval.

Expert opinion: For advanced disease, palliation and preserving patients QoL are still the primary goal of treatment. Therefore, differing toxicity profiles are often a deciding factor in first-line and also maintenance setting for non-squamous NSCLC.

Special attention is necessary to renal function and drugs’ nephrotoxicity. Moreover, it is to consider the specific AEs of drugs classes: hypertension, bleeding, and proteinuria, for anti-VEGF therapy; skin toxicity, diarrhea, interstitial lung disease for TKIs; vision disorders, and hepatotoxicity for ALK-inhibitor. It is important to select patients for a treatment on the basis of their comorbidities and the presence of risk factors.     

三维适形放疗联合培美曲塞治疗非鳞癌局部晚期肺癌的近期疗效及毒性反应

目的：观察三维适形放疗联合培美曲塞治疗非鳞癌局部晚期肺癌的近期疗效及毒性反应。方法：将2009年10月至2012年6月期间我院收治的非鳞癌局部晚期肺癌患者98例，将其随机分为观察组49例和对照组49例，观察组患者给予三维适形放疗联合培美曲塞进行治疗，对照组患者仅给予三维适形放疗，观察两组患者治疗的临床疗效及两组患者治疗后毒性反应的发生率。结果：两组患者经治疗后均取得一定的临床效果，观察组患者的有效率为63．3％明显高于对照组的32．7％，差异具有统计学意义（P＜0．05）；观察组患者毒性反应的发生率与对照组相比无显著差异（P＞0．05）。结论：三维适形放疗治疗非鳞癌局部晚期肺癌时应用培美曲塞能够显著提高患者的临床疗效，且用药后的毒性反应发生率没有增加，值得在临床普遍推广与应用。     

Maintenance treatment of combination with bevacizumab vs single agent for advanced non-squamous non-small cell lung cancer: A systematic review and meta-analysis

Background:When the patients of advanced non-squamous non-small cell lung cancer (NSCLC) have achieved remission by induction therapy, it is controversial that combination with bevacizumab is used as maintenance therapy. Pemetrexed is a classic drug for maintenance therapy, is bevacizumab the superiority to pemetrexed is also unclear. This meta-analysis aims to evaluate the effectiveness and safety of advanced non-squamous NSCLC in the maintenance treatment.Method:From the establishment as of December 6, 2020, PubMed, Embase, and Cochrane electronic databases were searched and the American Society of Clinical Oncology, European Society of Medical Oncology, and National Comprehensive Cancer Network databases in the past 10 years. The application of combination with bevacizumab, pemetrexed was studied in clinical trials of maintenance treatment for advanced NSCLC. The extracted data include progression-free survival (PFS), overall survival (OS), and grade 3–4 adverse events (AE).Results:Seven clinical trials we screened, 6 were phase III RCTs, and a cohort trial, including 3298 patients. Compared with bevacizumab and pemetrexed, PFS of combination with bevacizumab was significantly improved (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.65–0.77, P < .00001), but OS was not improved (HR = 0.93, 95% CI = 0.85–1.01, P = .10). Compared with bevacizumab and pemetrexed, no significant difference of PFS (HR = 0.87, 95% CI = 0.69–1.09, P = .21), and OS (HR = 0.87, 95% CI = 0.72–1.05, P = .15) was found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab (odds ratio = 1.63, 95% CI = 1.35–1.97, P < .00001).Conclusions:PFS was significantly improved in patients with advanced non-squamous NSCLC who use bevacizumab combination with single-agent as maintenance treatment, but it does not translate into the advantages of OS; compared with bevacizumab, no PFS and OS benefits were found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab than pemetrexed and bevacizumab.