Impact of G-CSF Prophylaxis on Chemotherapy Dose-Intensity,Link Between Dose-Intensity and Survival in Patients with Metastatic Pancreatic Adenocarcinoma

BackgroundIn metastatic pancreatic adenocarcinoma, few data are available on the use of granulocyte-colony stimulating factor (G-CSF) prophylaxis and its impact on dose-intensity (DI), or the link between DI and progression-free survival (PFS). This study assessed the impact of G-CSF prophylaxis on the DI received by patients and the relationship between full DI and PFS according to chemotherapy regimens.Patients and MethodsPatients from three first-line randomized phase II clinical trials were included in this retrospective cohort. G-CSF prophylaxis groups were identified and balanced according to baseline characteristics using a propensity score. Patients were classified into 2 treatment groups (FOLFIRINOX vs FOLFIRI/nab-paclitaxel (NAB)). DI was a binary variable (full/reduced). Adverse events were defined using NCI-CTCAE v4.0.ResultsOf the 498 patients, 154 (31%) were in “prophylaxis” group; 179 (36%) were treated by FOLFIRINOX and 319 (64%) by FOLFIRI/NAB. In FOLFIRINOX group, G-CSF prophylaxis was significantly associated with a higher rate of full DI (OR, 5.07; 95% CI, 1.52-16.90; P < .01) while in FOLFIRI/NAB group, it was significantly associated with a lower rate of full DI (OR, 0.23; 95% CI, 0.06-0.83; P = .03). Full DI was associated with a non-significant increase in PFS (FOLFIRINOX group: HR 0.83; 95% CI, 0.59-1.16; P = .27; FOLFIRI/NAB group: HR 0.84; 95% CI, 0.63-1.11; P = .22).ConclusionGranulocyte-colony stimulating factor prophylaxis was associated with a higher rate of full DI with FOLFIRINOX. Full DI was associated with a non-significant increase in PFS. These results need to be confirmed prospectively.     

N064A (Alliance): Phase II Study of Panitumumab,Chemotherapy, and External Beam Radiation in Patients with Locally Advanced Pancreatic Adenocarcinoma

BackgroundThis North Central Cancer Treatment Group (NCCTG) N064A (Alliance) phase II trial evaluated upfront chemoradiotherapy incorporating the EGFR inhibitor panitumumab, followed by gemcitabine and panitumumab for unresectable, non-metastatic pancreatic cancer.MethodsThe treatment consisted of fluoropyrimidine and panitumumab given concurrently with radiotherapy followed by gemcitabine and panitumumab for 3 cycles followed by maintenance panitumumab. The primary endpoint was the 12-month overall survival (OS) rate and secondary endpoints included confirmed response rate (RR), OS, progression-free survival (PFS), and adverse events. Enrollment of 50 patients was planned and the study fully accrued.ResultsFifty-two patients were enrolled, but only 51 were treated and included in the analysis. The median age of patients was 65 years and 54.9% were women. Twenty-two patients received at least 1 cycle of systemic therapy following radiotherapy, but 29 patients received chemoradiotherapy only without receiving subsequent chemotherapy after completion of chemoradiotherapy. The overall RR was 5.9% (95% CI: 1.2%-16.2%). The 12-month OS rate was 50% (95% CI: 38%-67%) which fell short of the per-protocol goal for success (51.1%). The median PFS was 7.4 months (95% CI: 4.5-8.6) and the median OS was 12.1 months (95% CI 7.9-15.9). Grade 3 or higher adverse events were reported by 88%.ConclusionThe combination of panitumumab, chemotherapy, and external beam radiation therapy was associated with very high rates of grades 3-4 toxicities and survival results did not meet the trial’s goal for success. This regimen is not recommended for further study (ClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT00601627","term_id":"NCT00601627"}}NCT00601627).     

肺肠型腺癌研究进展

肺肠型腺癌是与结直肠腺癌有相似组织形态的原发性肺腺癌,发病机制尚未明确,可能与癌细胞的肠型分化有关.肺肠型腺癌主要临床症状与普通型肺腺癌类似,包括咳嗽、咳血丝痰等,影像学表现亦相似,漏诊及误诊率高.其血清癌胚抗原和CA199水平显著高于普通型肺腺癌,但与肺转移性结直肠癌比较差异无统计学意义.肺肠型腺癌肠型分化成分＞50...     

金复康口服液对裸鼠人肺腺癌细胞凋亡相关基因表达的影响

目的探讨金复康口服液诱导裸鼠人肺腺癌LAX-83移植瘤细胞凋亡的作用及其分子机制。方法以LAX-83人肺腺癌瘤株在裸鼠皮下移植传代,将造模的裸鼠随机分为荷瘤对照组、金复康治疗组、顺氨氯铂(DDP)对照组。药物干预21d后,观察各组裸鼠瘤重及抑瘤率,并检测肿瘤组织中细胞凋亡情况及凋亡相关基因的蛋白表达。结果金复康治疗组抑瘤率为49.64%,平均瘤重与荷瘤对照组比较有显著差异(P<0.05),与DDP对照组比较无显著性差异(P>0.05);电镜下可见典型的早期凋亡细胞和凋亡小体。FCM检测细胞凋亡率为(17.51±3.56)%,TUNEL法观察凋亡细胞数为7.07±1.53,与荷瘤对照组及DDP对照组比较均有显著差异(P<0.01);免疫组化结果表明,金复康治疗组和DDP对照组均能降低Bcl-2基因蛋白表达,增加Bax和Fas基因蛋白表达,与荷瘤对照组比较P<0.01,两组对P53基因蛋白表达与荷瘤对照组比较,P>0.05。结论金复康口服液有诱导肿瘤细胞凋亡的作用,可降低Bcl-2基因蛋白表达,增加Bax和Fas基因蛋白表达。     

EGFR突变阳性肺腺癌患者多学科诊疗一例

本文介绍1例55岁女性肺腺癌患者从初诊、根治性手术、术后辅助治疗到远处转移后的多学科诊治过程.患者因右肺结节就诊,经多学科讨论后接受肺叶切除术,术后病理为腺癌,基因检测提示表皮生长因子受体(epidermal growth factor receptor,EGFR)基因敏感突变,患者接受多学科讨论的建议进行含铂双药辅助...     

铝碳酸镁对十二指肠液反流所致大鼠食管病变的防治作用

目的　通过动物实验 ,研究十二指肠液反流对食管上皮的损伤及评价铝碳酸镁对食管粘黏损伤的预防和治疗作用。方法　 16 0只SD大鼠 ,♂ ,2 0只为正常空白对照 (C组 ) ,14 0只行全胃切除 +食管空肠吻合术 ,术后 2周存活的大鼠随机分为A、B两组 ,A组予以铝碳酸镁管喂 ,B组管喂等量的生理盐水 ,术后 10周处死所有的大鼠 ,对食管上皮进行大体形态、病理学及电镜观察。结果　A、B两组的食管有程度不同的反流性食管炎 ,组织学表现为炎症、糜烂、溃疡、鳞状上皮增生、Barrett上皮化生及不典型增生。B组的炎症程度重于A组 (P <0 .0 1) ,Barrett上皮化生及不典型增生的发生率明显高于A组 (P <0 .0 5 )。B组有 1例食管微灶腺癌形成。扫描及透射电镜发现B组有Barrett化生的食管上皮典型分泌型肠上皮的特征。结论　铝碳酸镁能有效保护十二指肠液反流的食管粘黏 ,预防及治疗因其所致的多种病理学损害     

2011年版《英国药典》概览

目的简要介绍《英国药典》2011年版的基本情况、编排结构。方法分析比较了《英国药典》2011年版和2010年版的不同。结果与结论英国药典委员会每年都对《英国药典》进行更新和修订,值得学习和借鉴。     

阑尾原发性腺癌晚期形成Krukenberg瘤的临床分析

目的:探讨阑尾原发性腺癌晚期形成Krukenberg瘤的临床特点、诊断及治疗。方法:分析1例表现为Krukenberg瘤的阑尾原发性腺癌患者的临床资料,并复习相关文献。结果:阑尾原发性腺癌晚期转移形成Krukenberg瘤的病例较为罕见,并且缺乏特异性临床表现,极易漏诊、误诊,术前或术中即明确诊断者极少见,绝大多数是通过术后组织病理学诊断而最终确诊。右半结肠切除术是阑尾原发性腺癌的首选治疗方式,术后辅以化疗等综合治疗。结论:以Krukenberg瘤为首发表现的病例在寻找原发癌灶时应考虑到原发性阑尾恶性肿瘤的可能。术中对阑尾的仔细探查是必要的,若发现阑尾形态异常改变除了及时行阑尾切除,术中还应对其进行冰冻病理检查以提高术中确诊率,指导手术治疗。     

Quelle place pour la radiothérapie dans la prise en charge des cancers du pancréas localisés ?

At diagnosis, about 15% of patients with pancreatic cancer present with a resectable tumour, 50% have a metastatic tumour, and 25% a locally advanced tumor (non-metastatic but unresectable due to vascular invasion) or borderline resectable. Despite the technical progress made in the field of radiation therapy and the improvement of the efficacy of chemotherapy, the prognosis of these patients remains very poor. Recently, the role of radiation therapy in the management of pancreatic cancer has been much debated. This review aims to evaluate the role of radiation therapy for these patients.     

RNAi沉默肺腺癌A549细胞系PD-L1基因表达对其增殖和凋亡的影响

目的:沉默肺癌细胞系A549的程序性死亡配体1(programmed death ligand 1,PD-L1)基因,观察其对A549细胞增殖和凋亡的影响。方法:构建PD-L1 shRNA重组质粒p GPU6/PD-L1,并应用脂质体转染法将其转染入A549细胞。RT-PCR法检测PD-L1基因的表达;Western blotting法检测PD-L1蛋白的表达;MTT法检测p GPU6/PD-L1对A549细胞增殖的影响;AnnexinⅤ-FITC/PI双染法检测p GPU6/PD-L1对A549细胞凋亡的影响。结果:成功将p GPU6/PD-L1转染入A549细胞;RT-PCR结果显示p GPU6/PD-L1使A549细胞PD-L1基因表达水平降低;Western blotting结果显示p GPU6/PD-L1转染A549细胞使PDL1蛋白表达减少;MTT结果显示p GPU6/PD-L1能够抑制A549细胞增殖;AnnexinⅤ-FITC/PI双染法检测结果显示p GPU6/PD-L1能够诱导A549细胞凋亡。结论:p GPU6/PD-L1能够下调肺癌细胞A549 PD-L1的表达,抑制细胞增殖,并诱导细胞凋亡。