Phase 2 Trial of Gemcitabine,Cisplatin, plus Ipilimumab in Patients with Metastatic Urothelial Cancer and Impact of DNA Damage Response Gene Mutations on Outcomes

Background

Chemotherapy may exert immunomodulatory effects, thereby combining favorably with the immune checkpoint blockade. The pharmacodynamic effects of such combinations, and potential predictive biomarkers, remain unexplored.

吉西他滨联合5-Fu和CF治疗晚期乳腺癌

目的评价吉西他滨联合氟尿嘧啶(5-Fu)/甲酰四氢叶酸(CF)组成的GLF方案作为二线方案治疗晚期乳腺癌的疗效和毒性。方法38例既往曾接受蒽环类和/或紫杉类方案化疗的晚期乳腺癌患者,采用GLF双周方案,即吉西他滨1,200mg/m2静脉滴注,CF200mg/m2,经静脉滴注5-Fu 325mg/m2,先静脉推注,然后2.8mg/m2持续48h滴注;每2周重复1次,每2次为1周期。结果38例中CR2例、PR14例、NC13例、PD9例,总有效率为42.1%。Ⅲ～Ⅳ度白细胞下降为18.42%,Ⅲ度血小板下降为7.91%,Ⅲ度粒膜炎10.5%,其他不良反应轻微。结论吉西他滨联合5-Fu及CF组成GLF双周方案作为二线方案对蒽环类和/或紫杉类方案耐药的晚期乳腺癌疗效令人满意,不良反应少,值得进一步研究。     

Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer

BackgroundNeoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.MethodsData on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.ResultsPatients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).ConclusionsRepresenting one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.     

Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

AIM：To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS： We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS： Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, respectively.CONCLUSION： Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases.     

吉西他滨对人胰腺癌Patu-8988细胞株APE/Ref-1的诱导作用

目的:研究人胰腺癌细胞株在吉西他滨化疗时APE/Ref-1基因表达的变化,并试图揭示其在胰腺癌化疗耐药中所起的作用.方法:不同浓度吉西他滨0、10、20、40及60μmol/L作用人胰腺癌Patu-8988细胞株24 h,分别以RT-PCR及Western blot方法测定作用后APE/Ref-1的mRNA及蛋白表达情况.结果:吉西他滨作用人胰腺癌Patu-8988细胞株24h后,APE/Ref-1的mRNA及蛋白表达水平明显上升,并与吉西他滨的浓度呈正相关(RT-PCR:r=0.645,P=0.012;Western blot:r= 0.598,P=0.020).结论:APE/Ref-1在胰腺癌化疗时表达明显增强,可能与化疗耐药性的产生有关,并提示针对APE/Ref-1的靶向干预可能有助于提高胰腺癌的化疗敏感性.     

Poorly differentiated endocrine carcinoma of the pancreas responded to gemcitabine: Case report

Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further treatment recommendations. In this report, we describe a case of pancreatic PDEC treated with gemcitabine as third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered etoposide plus cisplatin as first-line treatment; he then received irinotecan for tumor relapse. However, because irinotecan induced ileus in this patient, we chose gemcitabine as thirdline chemotherapy. After two cycles of gemcitabine (1000 mg/m2 on days 1, 8 and 15 every 4 wk), a partialtumor response was noted by computed tomography (approximately 68% reduction in tumor size). Our patient survived for 15 mo after diagnosis. This is a rare case of unresectable pancreatic PDEC, which showed a partial response to gemcitabine after the failure of two other regimens. Gemcitabine could be an effective treatment option for pancreatic PDEC that is resistant to other treatments.     

肝动脉药物灌注加化疗栓塞治疗胆囊癌肝转移疗效评价

目的评价肝动脉药物灌注加化疗栓塞治疗胆囊癌肝转移患者临床价值。方法30例胆囊癌肝转移患者均采用肝动脉药物灌注加化疗栓塞,共介入治疗110周期,化疗药物为吉西他滨＋顺铂,栓塞剂采用超液化碘油。所有患者每次介入治疗前均行增强CT测量肿瘤大小,采用RECIST标准评价疗效。采用Kaplan-Meier计算生存率。随访期限直至患者死亡。结果本组患者完全缓解（CR）3%（1例）,部分缓解（PR）50%（15例）,病变稳定（SD）20%（6例）,病变进展（PD）27%（8例）,总有效率（CR＋PR）53%（16例）。1年生存率60%,2年生存率20%。介入治疗始中位生存期13月,中位无进展生存期11月。结论肝动脉药物灌注加化疗栓塞是治疗无法手术切除胆囊癌肝转移患者的有效方法。     

香菇多糖联合GP方案治疗晚期非小细胞肺癌25例

目的评价香菇多糖联合吉西他滨和顺铂（GP方案）治疗晚期非小细胞肺癌（NSCLC）的近期疗效及对患者生活质量的影响。方法将51例ⅢB和Ⅳ期NSCLC患者随机分为治疗组25例和对照组26例,均给予吉西他滨1 000 mg&#8226;（m2）－1,第1,8天静脉滴注;顺铂25 mg&#8226;（m2）－1,第2～4天静脉滴注。21 d为1个周期,两个周期后评价疗效。治疗组同时给予香菇多糖2 mg＋ 5%葡萄糖注射液或0.9%氯化钠注射液250 mL,第1,4天静脉滴注。两组化疗前均给予5 羟色胺受体拮抗药预防性止吐,并常规给予水化利尿处理。结果两组QLQ C30生活质量评分均较治疗前升高,治疗组整体生活质量评分显著高于对照组,乏力较对照组显著改善（P＜0.05）;两组QLQ LC 13肺癌相关症状（咳嗽、呼吸困难、胸痛）评分较治疗前均下降;治疗组细胞免疫功能较治疗前无变化,对照组免疫功能下降,两组治疗后比较差异有统计学意义（P＜0.05）;对照组白细胞减少多于治疗组。结论香菇多糖联合GP方案化疗治疗晚期非小细胞肺癌可有效控制NSCLC进展,减轻化疗不良反应,预防患者细胞免疫功能损伤,明显改善患者的生活质量。     

Gemcitabine-releasing polymeric films for covered self-expandable metallic stent in treatment of gastrointestinal cancer

Non-vascular drug-eluting stents have been studied for the treatment of gastrointestinal cancer and cancer-related stenosis. In this study, we designed and evaluated a gemcitabine (GEM)-eluting covered nonvascular stent. Polyurethane (PU)/polytetrafluoroethylene (PTFE) film was selected for the drug loading and eluting membrane. The membrane was fabricated by dip-coating on a Teflon bar (∅; 10 mm), air-dried, peeled off and applied to a self-expanding Nitinol stent. Various amounts of poloxamer 407 (PL, Lutrol^® F127, BASF) (8%, 10%, or 12% of PU by weight) were added to control the release of GEM from membranes. The membrane containing 12% PL (GEM-PU-PL12%) showed the most favourable release properties; 70% of the loaded GEM released within 35 days, including the 35% released during the initial burst. The biological activities of GEM-PU-PL12% were evaluated using human cholangiocarcinoma cells (SK-ChA-1). GEM-PU-PL12% most efficiently inhibited the proliferation of cholangiocarcinoma cells and most highly induced pro-inflammatory cytokines (TNF-α, IL-1β and IL-12) and p38 MAPKs in the cells. Subtumoural insertion of the GEM-PU-PL12% membrane more efficiently inhibited the growth of CT-26 colon cancer than other membranes. In this study, the GEM-eluting metal stents covered with PU-PL12% showed considerable feasibility for the treatment of malignant gastrointestinal cancer as well as cancer-related stenosis.