白蛋白结合型紫杉醇一线治疗晚期胰腺癌的疗效与安全性

目的:探讨白蛋白结合型紫杉醇(Nab-P)治疗晚期胰腺癌的疗效与安全性。方法:回顾性分析2012年10月至2014年12月98例晚期胰腺癌患者的临床资料,根据是否一线接受Nab-P化疗分为Nab-P组和对照组,其中Nab-P组58例,对照组40例。Nab-P组中,11例接受Nab-P联合吉西他滨治疗,47例接受Nab-P联合替吉奥治疗;对照组中,18例接受吉西他滨+顺铂化疗,22例接受替吉奥治疗。每2个周期评价疗效,每周期评价不良反应。观察患者的近期疗效、PFS、OS及不良反应。结果:两组患者年龄、性别、转移灶数目及既往治疗等基线资料无明显差异（P＞0.05）。Nab-P组的ORR和DCR均明显高于对照组（ORR:53.4% vs 25%,P＜0.05;DCR:96.6% vs 50%）。Nab-P组中位PFS为5.6个月,对照组中位PFS为3.3个月;Nab-P组中位OS为10.5个月,对照组中位OS为5.3个月。经log-rank分析,Nab-P组的PFS、OS均明显长于对照组（P＜0.05）。两组III级及以上血液学毒性、恶心、呕吐、乏力及周围神经毒性的发生率无明显统计学差异。结论:采用白蛋白结合型紫杉醇与化疗结合治疗晚期胰腺癌可以提高患者的生存时间,安全性好。     

白蛋白结合型紫杉醇联合替吉奥治疗吉西他滨治疗失败进展期胰腺癌的临床观察

背景与目的:化疗是晚期胰腺癌患者的主要治疗手段,但目前尚没有二线治疗晚期胰腺癌的标准方案。本研究旨在评估白蛋白结合型紫杉醇联合替吉奥二线治疗吉西他滨治疗失败进展期胰腺癌的近期疗效和安全性。方法:19例接受吉西他滨一线治疗失败的晚期胰腺癌患者,应用白蛋白结合型紫杉醇联合替吉奥二线治疗。白蛋白结合型紫杉醇用药剂量125 mg/m2,静脉滴注30 min,第1、8天给药;替吉奥胶囊40 mg,口服,每日2次,第1~14天;每3周重复。结果:所有患者均可评价疗效,其中完全缓解(complete response,CR)1例,部分缓解(partial response,PR)4例,疾病稳定(stable disease,SD)9例,客观有效率(objective response rate,ORR)为26.3%,疾病控制率(disease control rate,DCR)为73.7%,中位无进展生存期(progression free survival,PFS)为5.2个月。主要不良反应包括血液学毒性、肌肉关节酸痛、消化道反应、感觉神经病变、疲乏和脱发等。结论:白蛋白结合型紫杉醇联合替吉奥方案二线治疗既往吉西他滨治疗失败进展期胰腺癌疗效确切,且不良反应可以耐受。     

白蛋白结合型紫杉醇联合吉西他滨一线治疗晚期胰腺癌的疗效观察

目的 探讨白蛋白结合型紫杉醇联合吉西他滨一线治疗晚期胰腺癌的疗效和安全性。方法 本院2012年3月至2015年1月收治的27例经病理确诊为晚期转移性胰腺癌患者,接受白蛋白结合型紫杉醇联合吉西他滨一线治疗,具体方案：白蛋白结合型紫杉醇125 mg／m²静滴,d₁、d₈;吉西他滨1000 mg／m²静滴,d₁、d₈,每21天为1个周期。2个周期后按照RECIST 1.1版标准评价客观疗效,采用国立癌症研究所毒性判定标准（NCI CTC）3.0评价化疗毒性反应,同时随访其生存情况并比较不同临床病理特征的中位无进展生存期（PFS）和总生存期（OS）。结果 所有患者均可评价疗效,无CR病例,PR 2例,SD 19例,有效率（RR）和疾病控制率（DCR）分别为 7.4％和77.8％。全组患者的中位PFS和OS分别为5.0个月（95%CI：4.0～6.7个月）和8.0个月（95%CI：7.5～13.8个月）。亚组分析显示化疗周期数与患者的PFS和OS有关。主要不良反应为恶心呕吐（48.1％）、疲劳（55.5％）、发热（7.4％）、皮疹（3.7％）及周围神经异常（11.1％）;严重不良反应主要为骨髓抑制,其中3～4级血液学毒性包括白细胞减少、血小板减少和血红蛋白减少。结论白蛋白结合型紫杉醇联合吉西他滨治疗国人晚期胰腺癌疗效确切,不良反应可以耐受。     

白蛋白紫杉醇二线治疗晚期胰腺癌的临床观察

目的:探讨白蛋白紫杉醇二线治疗一线含吉西他滨方案化疗失败的晚期胰腺癌患者的疗效和安全性。方法:6例一线含吉西他滨方案化疗失败的晚期胰腺癌患者,给予白蛋白紫杉醇100mg/m2 静脉滴注,d1、d8、d15,28天为1周期。治疗至疾病进展或出现不可耐受的不良反应。根据实体瘤疗效反应评价标准(RECIST)评价疗效,常规毒性判定标准(NCI-CTC 3.0)评价不良反应。结果:6例患者中位治疗时间为2周期（1~8周期）,无CR病例,PR 1例,SD 3例,PD 2例。总有效率为16.7%,疾病控制率为66.7%,中位无疾病进展时间（PFS）为5.3个月,中位总生存时间（OS）为7个月,有2例患者仍存活,随访至今,生存时间分别为54个月和58个月。不良反应主要为骨髓抑制和神经毒性,多为Ⅰ-Ⅱ级,其中1例患者出现Ⅲ级白细胞下降,4例Ⅱ级下降;2例出现Ⅱ级肌肉酸痛,无Ⅳ级不良反应。结论:对于一线含吉西他滨方案化疗失败的晚期胰腺癌患者,白蛋白紫杉醇单药方案化疗可取得一定疗效,患者耐受性好,值得扩大样本量进一步研究。     

白蛋白结合型紫杉醇联合替吉奥一线治疗老年晚期胰腺癌患者的临床观察

目的:探讨白蛋白结合型紫杉醇联合替吉奥方案一线治疗老年晚期胰腺癌患者的疗效及安全性。方法:回顾性分析2014年10月至2016年10月解放军总医院28例接受白蛋白结合型紫杉醇联合替吉奥方案一线化疗的晚期转移性胰腺癌老年患者(年龄≥60岁)的临床资料。根据NCI-CTC3.0标准每周期评价不良反应,依据实体肿瘤RECIST标准每2周期评估疗效,并随访其生存情况。结果:接受白蛋白结合型紫杉醇联合替吉奥方案一线化疗的28例患者的ORR为42.9%（12/28）,DCR为82.1%（23/28）。接受治疗的28例患者的中位PFS为9.4个月(95%CI:6.1～12.7个月),中位OS为12.6个月（95%CI:7.6～17.5个月）。不良反应发生情况:白细胞减少（71.4%）、恶心呕吐（53.6%）、脱发（46.4%）、感觉神经异常（53.6%）。Ⅲ-Ⅳ度不良反应包括白细胞减少（21.4%）、脱发（3.6%）、口腔黏膜炎（3.6%）、感觉神经异常（3.6%）。结论:白蛋白结合型紫杉醇联合替吉奥方案一线治疗老年晚期胰腺癌疗效较好,不良反应可耐受。     

经动脉持续灌注化疗治疗中晚期胰腺癌的临床分析

 目的 比较经动脉持续灌注化疗和全身静脉化疗治疗中晚期胰腺癌的临床疗效，探讨选择性动脉持续灌注化疗的临床应用价值。方法 51例中晚期胰腺癌，其中25例采用经动脉持续灌注吉西他滨和5-Fu方案，26例采用经外周静脉灌注吉西他滨和5-Fu方案。应用世界卫生组织实体瘤疗效评定标准评价疗效，肿瘤体积测量采用MRI或CT。使用临床受益反应（CBR）对疼痛、体力状况及体重改变情况作出综合评价。采用WH0抗肿瘤药物急性与亚急性毒性分级标准对不良反应进行评价。结果 动脉灌注化疗组的有效率（32．0％）高于外周静脉化疗组（23．1％），但差异无显著性。动脉灌注化疗组的临床受益率（80．0%）高于外周静脉化疗组（50．0％），差异有显著性。6个月、9个月、1年的累积生存率和中位生存时间，动脉灌注化疗组高于外周静脉化疗组，差异有显著性。按WHO分级标准，两组患者不良反应之间无显著性的差异。结论 经动脉持续灌注吉西他滨和5-Fu较外周静脉灌注吉西他滨和5-Fu能提高中晚期胰腺癌的临床受益率和生存期，其方法安全可靠，且不良反应少。     

胰腺癌肝转移治疗进展

胰腺癌肝转移（pancreatic cancer with liver metastases,PCLM）为临床难治性恶性肿瘤,其起病隐匿、进展迅速、预后极差,仅极少数患者具有手术机会。全身化疗为主要治疗手段,FOLFIRINOX方案（氟尿嘧啶、奥沙利铂、伊立替康和亚叶酸钙）已成为体能状况良好的PCLM患者的一线化疗方案。以吉西他滨为基础的化疗仍居重要地位,其中吉西他滨联合白蛋白结合型紫杉醇凸显优势,成为PCLM一线化疗的新标准。吉西他滨联合分子靶向治疗的研究暂无新的突破。全身化疗联合经动脉灌注化疗栓塞（transcatheter arterial chemoembolization,TACE）有可能改善PCLM患者的生存率,尚需进一步开展前瞻性的随机对照临床试验加以证实。射频消融（radio frequency ablation,RFA）、近距离放疗栓塞术等尚处探索阶段。基于化疗、放疗与中草药的多学科综合治疗模式方兴未艾。本文就PCLM的治疗进展进行综述。      

卡培他滨节拍化疗在转移性结直肠癌维持治疗中的探索性Ⅱ期研究

背景与目的：转移性结直肠癌患者一线诱导化疗后的维持治疗方案如何选择，尚存在争议。本研究将卡培他滨节拍化疗应用于转移性结直肠癌维持治疗，评估其疗效与安全性。方法：本研究是单臂、单中心探索性研究。接受一线诱导化疗（XELOX、mFOLFOX6、FOLFIRI）18~24周的转移性结直肠癌患者，评估为临床获益后接受卡培他滨500 mg，每天2次口服维持治疗，直至疾病进展。研究首要终点是无进展生存期（progression-free survival，PFS），包括卡培他滨维持治疗的PFS和诱导化疗续贯维持治疗的PFS。次要终点为总生存期（overall survival，OS）和不良反应。结果：2014年10月16日—2017年12月31日于上海交通大学医学院附属瑞金医院接受治疗的转移性结直肠癌患者37例接受节拍化疗维持治疗。中位随访时间15.0个月（4.0~41.4个月）。节拍化疗维持治疗的中位PFS为5.6个月（1.7~38.5个月），诱导化疗续贯维持治疗的中位PFS为11.4个月（6.8~44.3个月）。主要的不良反应为白细胞减少（8/37，21.6%）、恶心呕吐（5/37，13.5%）和手足综合征（3/37，8.1%）。没有1例患者出现3~4级严重不良反应。结论：卡培他滨节拍化疗应用于转移性结直肠癌诱导化疗后维持治疗安全、有效。     

白蛋白结合型紫杉醇联合替吉奥治疗晚期胰腺癌的研究进展

胰腺癌早期症状隐匿,恶性程度高,是消化系统常见的恶性肿瘤之一。外科手术是延长胰腺癌患者生存期的最佳选择,但只有15%~20%的胰腺癌患者能接受手术治疗。其余患者因局部晚期或全身转移,只能进行以内科治疗为主的综合治疗。目前晚期胰腺癌患者的首选治疗方式是以吉西他滨为基础的化疗,但仅使晚期胰腺癌患者的平均生存期延长为5.5~7个月,疗效有限。近几年,多项研究证实白蛋白结合型紫杉醇联合替吉奥治疗晚期胰腺癌可以提高患者的PFS和OS（分别为6.2个月和13.6个月）。治疗过程中最常出现的不良反应是中性粒细胞减少,但未出现因不良反应而停止治疗或死亡的现象。为晚期胰腺癌患者的治疗带来了新希望。本文将总结白蛋白结合型紫杉醇联合替吉奥在治疗晚期胰腺癌中的相关研究。     

TX方案治疗铂类治疗失败的进展期胃癌的临床疗效分析

目的：评价紫杉醇联合卡培他滨作为含铂类药物治疗失败的进展期胃癌二线治疗的疗效及安全性。方法：既往接受FP或者FOLFOX4方案化疗的进展期胃癌患者36例,采用TX方案化疗,紫杉醇145mg/m2静脉滴注3h,d1;卡培他滨2000mg/m2,分2次口服,d1-14,21天为一个周期,随访观察疗效,不良反应,进展时间和生存期。结果：36例患者共接受142个周期的化疗,中位化疗周期数4个。全组36例患者中有35例可评价疗效及不良反应,其中8例部分缓解,有效率为22.8%（95%CI：8.2%-37.5%）。中位进展时间和生存时间分别为4.8个月（95%CI：2.9-6.2）和8.1个月（95%CI：6.4-12.7）。Ⅲ/Ⅳ度不良反应主要为骨髓抑制、手足综合征及脱发。结论：紫杉醇联合卡培他滨方案二线治疗进展期胃癌疗效确切,不良反应小,尤其对老年患者耐受性好。     

晚期胰腺癌常用一线化疗方案真实世界临床疗效观察

目的:比较白蛋白结合型紫杉醇联合吉西他滨(AG)、白蛋白结合型紫杉醇联合替吉奥(AS)、吉西他滨联合奥沙利铂(GEMOX)、吉西他滨联合替吉奥(GS)方案在真实世界一线治疗晚期胰腺癌的有效性及安全性。方法:回顾性分析2016年1月至2021年6月于我院诊治的165例晚期胰腺癌患者的病例资料,根据化疗方案不同分为四组：AG组(n=40)、AS组(n=31)、GEMOX组(n=31)、GS组(n=63),按照实体肿瘤临床疗效评价标准(RECIST)1.1版本评估临床疗效和常见不良事件评价标准(CTCAE)5.0版本评估患者的不良反应,主要研究终点为总生存期(overall survival, OS)和无进展生存期(progression-free survival, PFS),次要研究终点为客观缓解率(objective response rate, ORR)和疾病控制率(disease control rate, DCR)以及治疗相关不良反应,采用Cox风险比例模型分析影响患者预后的因素。结果:165例患者的中位OS时间为10.5个月,中位PFS时间为6.0个月,AG、AS、GEMOX、...     

结直肠癌肝转移患者经微波消融联合肝动脉栓塞化疗的效果和肝功能变化情况

目的探讨微波消融术(MWA)联合肝动脉化疗栓塞术(TACE)治疗结直肠癌肝转移中的临床疗效及其患者肝功能变化、生存情况以及生活质量评价。方法回顾性分析80例结直肠癌肝转移患者的临床相关资料,其中有38例单独行肝动脉化疗栓塞术治疗,为TACE组;其他42例行微波消融联合肝动脉栓塞化疗进行治疗,为MWA+TACE组。对2组的临床疗效、患者肝功能变化、生存情况以及生活质量评价数据进行整理分析。结果 TACE组和MWA+TACE组的临床有效率分别是39.5%和76.2%,MWA+TACE组患者的临床疗效显著优于TACE组患者(χ~2=11.098,P≈0.001)。2组患者的血清白蛋白、谷丙转氨酶、总胆红素含量等肝功能各项指标不存在统计学差异(P>0.05)。MWA+TACE组患者的2年、3年生存率显著高于TACE组(P<0.05)。在治疗6个月后,MWA+TACE组患者的生理状况、功能状况、情感状况、家庭/社会状况均显著高于TACE组患者(P<0.05);在总体评分上,MWA+TACE组患者显著优于TACE组(P<0.05)。结论微波消融联合肝动脉栓塞化疗治疗结肠癌肝转移有非常显著的效果,相对于单独化疗,能够延长患者的生存时间以及提高其生活质量,且对肝功能不会造成损害。     

吉西他滨单药或联合白蛋白结合型紫杉醇治疗东亚人群晚期胰腺癌临床疗效的荟萃分析

目的 系统评价吉西他滨单药和吉西他滨联合白蛋白结合型紫杉醇一线治疗东亚人群晚期转移性胰腺癌的疗效，以期为中国转移性胰腺癌临床一线治疗的合理用药提供依据。方法 按照预设的纳入和排除标准，在万方、Cochran Library、MEDLINE、PubMed和CNKI等数据库中系统性检索2010年1月至2018年6月发表的文献。主要观察终点为客观缓解率（ORR）， 次要终点为无进展生存期（PFS） 和总生存期（OS）。提取纳入文献的相关资料，采用Rav Man 3.5.0版软件进行Meta分析。结果 共纳入38项研究，合计1945例患者。吉西他滨单药治疗晚期胰腺癌的ORR为0.15（95％CI：0.11～0.18）、中位PFS为3.39（95％CI：2.74～4.05）个月、中位OS为7.39（95％CI：6.54～8.23）个月；吉西他滨联合白蛋白结合型紫杉醇治疗晚期胰腺癌的ORR为0.40（95％CI：0.29～0.52）、中位PFS为5.68（95％CI：4.30～7.06）个月、中位OS为9.80（95％CI：7.89～11.71）个月。结论 吉西他滨联合白蛋白结合型紫杉醇与吉西他滨单药比较， 具有明显的优效性，适合东亚人群，特别是中国晚期胰腺癌患者。     

Real World First-Line Treatments and Outcomes of Nab-Paclitaxel Plus Gemcitabine,mFOLFIRINOX and GEMOX in Unresectable Pancreatic Cancer from a Chinese Single Institution

Background: There have not been any head-to-head prospective studies to compare the effects of different chemotherapy regimens as first-line treatments for unresectable pancreatic cancer (UPC). We aimed to compare the effectiveness of nab-paclitaxel plus gemcitabine, mFOLFIRINOX and gemcitabine plus oxaliplatin (GEMOX) as first-line treatments by using real-world data from Chinese patients. Methods: We retrospectively included patients with UPC treated with nab-paclitaxel plus gemcitabine, mFOLFIRINOX or GEMOX as a first-line treatment at Sun Yat-sen University Cancer Center. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed. Results: A total of 117 patients were administered nab-paclitaxel plus gemcitabine (n = 62), mFOLFIRINOX (n = 30) or GEMOX (n = 25) as first-line chemotherapy. The median OS was 11.1, 10.1 and 10.2 months (p = 0.75) in the nab-paclitaxel plus gemcitabine, mFOLFIRINOX and GEMOX, respectively. The ORR was similar among the three groups (24%, 23% and 32%, p = 0.76) and the DCR was higher in the nab-paclitaxel-gemcitabine group (82%) than the other two groups (60% and 64%, p = 0.04). The most common adverse events of grade 3 or 4 were neutropenia (32%, 28% and 5%), peripheral neuropathy (13%, 16% and 0) and fatigue (9%, 16% and 5%). Febrile neutropenia occurred in 2%, 4% and 5% of the patients in the three groups. Conclusion: In the first line treatment of UPC, our results suggest that nab-paclitaxel plus gemcitabine was associated with a higher DCR than mFOLFIRINOX or GEMOX, while all groups demonstrated similar OS, PFS and ORR.     

Neglected geriatric assessment and overtreatment of older patients with pancreatic cancer - Results from a prospective phase IV clinical trial

BackgroundOlder patients with metastatic pancreatic cancer may suffer increased toxicity from intensive chemotherapy. Treatment individualization by geriatric assessment (GA) might improve functional outcome.MethodsWe performed a multicenter, phase IV, open label trial in patients ≥70 years with metastatic pancreatic adenocarcinoma. Patients underwent GA and were assigned to one of three categories based on their scores: Go-Go, Slow-Go, or Frail. These categories were intended to guide physician's treatment decisions when choosing to treat patients with nab-paclitaxel/gemcitabine (arm A), gemcitabine (arm B), or best supportive care (arm C). Primary objective was a stable (loss of five points or less) Barthel's Activities of Daily Living (ADL) score during chemotherapy; secondary endpoints included GA scores during therapy, safety, quality of life, response and survival rates.ResultsThirty-two patients were enrolled in the trial in six centers in Germany (out of 135 planned), resulting in termination due to low recruitment. Fifteen patients were allocated to nab-paclitaxel/gemcitabine, fifteen to gemcitabine, and two to best supportive care by their physicians, although according to their GA scores 29 patients (91%) were categorized as Slow-Go and three (9%) as Go-Go. Thus, fifteen of 32 (47%) patients were misclassified and given a course of treatment inconsistent with their GA scores. Median progression-free survival (PFS) were 3.3 months and 9.1 months and median time to quality-of-life deterioration 13 days and 29 days in the nab-paclitaxel/gemcitabine and gemcitabine monotherapy arms, respectively. Serious adverse events were reported in 11 (78.6%) patients in the nab-paclitaxel/gemcitabine and 8 (53.3%) patients in the gemcitabine arm.ConclusionsClinical evaluations by investigators differed markedly from geriatric assessments, leading to potential overtreatment. In our modest sample size study, those patients undergoing more intensive therapy had a less favorable course.     

Advanced pancreatic carcinoma showing a complete response to arterial infusion chemotherapy

We report a patient with advanced carcinoma of the pancreatic body and tail with multiple liver metastases who showed a complete response to hepatic and splenic arterial infusion chemotherapy (HSAIC) with gemcitabine and 5-fluorouracil, following transcatheter peripancreatic arterial embolization (TPPAE) and partial splenic embolization (PSE). Nonresectable advanced pancreatic carcinoma tends to have a low response to medical treatment, with the median survival time being 6 months or less for stage IV cases. We disclose herein that the median survival time of patients receiving HSAIC after TPPAE is more than three times longer than the survival time attained with conventional treatments. However, in patients with advanced carcinoma of the pancreatic tail, for which TTPAE is not applicable, survival times remain low. Thus, in the patient described here, we also performed embolization of the left gastric and short gastric arteries as well as PSE to increase the flow within the great pancreatic and caudal pancreatic arteries via the splenic artery, and gemcitabine and 5-fluorouracil were administered via the splenic artery. As a result of these procedures, marked reduction in the advanced carcinoma of the pancreatic body and tail and of liver metastases was attained.     

Novel adjuvant therapies for pancreatic adenocarcinoma

Contemporary adjuvant therapy for pancreatic cancer patients following surgical resection includes chemotherapy and chemoradiotherapy. However, the median survival remains approximately 20 months despite multi-modality treatment using gemcitabine or fluoropyrimidine systemic chemotherapy. Adjuvant randomized trials are currently underway to evaluate cytotoxic combinations found to be active in advanced disease including FOLFIRINOX, gemcitabine/nab-paclitaxel and gemcitabine/capecitabine. Immunotherapy using genetically engineered cell-based vaccines had shown promise in resected pancreatic cancer patients during early phase trials, and algenpantucel-L vaccine is currently being evaluated in adjuvant setting in a randomized trial. This review focuses on novel adjuvant therapies currently in clinical evaluation.     

SEOM Clinical Guideline for the treatment of pancreatic cancer (2016)

Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future.     

Tumour–stroma interactions in pancreatic ductal adenocarcinoma: Rationale and current evidence for new therapeutic strategies

Most patients with pancreatic cancer present with advanced/metastatic disease and have a dismal prognosis. Despite the proven albeit modest benefits of gemcitabine demonstrated over a decade ago, subsequent advances have been slow, suggesting it may be time to take a different approach. It is thought that some key characteristics of pancreatic cancer, such as the desmoplasia, restricted vasculature and hypoxic environment, may prevent the delivery of chemotherapy to the tumour thereby explaining the limited benefits observed to-date. Moreover, there is evidence to suggest that the stroma is not only a mechanical barrier but also constitutes a dynamic compartment of pancreatic tumours that is critically involved in tumour formation, progression and metastasis. Thus, targeting the stroma and the tumour represents a promising therapeutic strategy. Currently, several stroma-targeting agents are entering clinical development. Among these, nab-paclitaxel appears promising since it combines cytotoxic therapy with targeted delivery via its proposed ability to bind SPARC on tumour and stromal cells. Preclinical data indicate that co-treatment with nab-paclitaxel and gemcitabine results in stromal depletion, increased tumour vascularization and intratumoural gemcitabine concentration, and increased tumour regression compared with either agent alone. Phase I/II study data also suggest that a high level of antitumor activity can be achieved with this combination in pancreatic cancer. This was recently confirmed in a Phase III study which showed that nab-paclitaxel plus gemcitabine significantly improved overall survival (HR 0.72) and progression-free survival (HR 0.69) versus gemcitabine alone for the first-line treatment of patients with metastatic pancreatic cancer.     

Retrospective Cohort Study of Caveolin-1 Expression as Prognostic Factor in Unresectable Locally Advanced or Metastatic Pancreatic Cancer Patients

Caveolin-1 (Cav-1) plays a key role in various neoplastic diseases and is upregulated in different cancers, including pancreatic ductal adenocarcinoma (PDAC). Furthermore, Cav-1 is critical for the uptake of albumin as well as nab-paclitaxel in PDAC cells. Here, we investigated the prognostic impact of Cav-1 expression in a cohort of 39 metastatic PDAC patients treated with different first-line chemotherapy regimens. We also assessed the predictive value of Cav-1 in patients treated with gemcitabine and nab-paclitaxel. Cav-1 expression was evaluated by immunohistochemistry staining in neoplastic and stromal cells, using metastatic sites or primary tumor tissue specimens. Higher levels of Cav-1 expression were associated with significantly worse overall survival (OS) and progression-free survival (PFS). No differences in OS were found between patients treated with gemcitabine + nab-paclitaxel vs. other chemotherapy options. Multivariate analysis for OS and PFS confirmed the independent prognostic role of Cav-1 expression. Our study evidenced a negative prognostic role of Cav-1 in patients affected by metastatic/locally advanced unresectable PDAC. Moreover, Cav-1 expression seems not to predict different response rates to different types of first-line treatment. Future prospective trials will be necessary to confirm the prognostic role of Cav-1 and explore Cav-1 specific inhibitors as a therapeutic option for advanced PDAC patients.