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| 1 | Metastasized pancreatic carcinoma with neoadjuvant FOLFIRINOX therapy and R0 resection显示文摘Patients with metastasized carcinoma of the pancreas have a very poor prognosis, and long-term survival cannot be expected. This case report describes two patients with an initial diagnosis of metastatic pancreatic cancer, both with hepatic metastases and one with an additional peritoneal carcinomatosis. Initially, both patients were treated intravenously with the FOLFIRINOX chemotherapy regimen, consisting of 5-FU, folinic acid, irinotecan and oxaliplatin. Surprisingly, the FOLFIRINOX treatment resulted in complete resolution of the hepatic metastases in both patients, with no lesions detectable by computed tomography scan. Furthermore, treatment response included decreased diameter of the primary tumor in the tail of the pancreas and disappearance of the additional peritoneal carcinomatosis. Both patients were discussed by our multidisciplinary tumor board, which recommended surgical resections of the carcinoma. The R0 resection of the primary tumor was successful in both cases and, interestingly, the resected tissues showed no evidence of the hepatic metastases intraoperatively. In the first case, the patient received a postoperative 6-mo course of adjuvant chemotherapy with gemcitabine. In the second case, the patient continued to receive the FOLFIRINOX regimen for an additional 6 mo postoperatively. At 12 mo after the operation, a nonresectable retroperitoneal lymph node metastasis was detected in the first patient, whereas the second patient remained in complete remission at the time of this report(5 mo after the adjuvant therapy was discontinued). This case report is the first of its kind to describe two cases of hepatic metastatic pancreatic carcinoma that were resectable following treatment with FOLFIRINOX. Further studies are required to examine the role of FOLFIRINOX as a neoadjuvant treatment option in subgroups of patients with initially metastasized pancreatic carcinoma. | Sophie Schneitler Patric Krpil Jasmin Riemer Gerald Antoch Wolfram Trudo Knoefel Dieter Hussinger Dirk Graf | 2015 | World Journal of Gastroenterology2015,21,20: | 9 |
| 2 | Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions显示文摘Pancreatic cancer(PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor. Recently PDAC stroma has been addressed as a potential therapeutic target. Nano albumin bound(Nab)-paclitaxel is an innovative molecule depleting tumor stroma, through interaction between albumin and secreted protein acidic and rich in cysteine. Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phase Ⅲ study. This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules. Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC. In this article, we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research. Furthermore, we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials. | Guido Giordano Massimo Pancione Nunzio Olivieri Pietro Parcesepe Marianna Velocci Tania Di Raimo Luigi Coppola Giuseppe Toffoli Mario Rosario D’Andrea | 2017 | World Journal of Gastroenterology2017,23,32: | 7 |
| 3 | Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer显示文摘AIM To directly compare the efficacy and toxicity of standarddose FOLFIRINOX(sFOLFIRINOX) and modified-dose FOLFIRINOX(mFOLFIRINOX, 75% of standard-dose) for pancreatic cancer.METHODS One hundred and thirty pancreatic cancer patients who received sFOLFIRINOX(n = 88) or mFOLFIRINOX(n = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate(ORR),disease control rate(DCR), progression-free survival(PFS), and overall survival(OS) were evaluated and compared using Pearson's chi-square test, Kaplan-Meier plot and log-rank test. The adverse events(AEs) were evaluated, and severe(≥ grade 3) AEs rates of the two groups were compared for toxicity analysis.RESULTS The mFOLFIRINOX group included more female patients(30.7% vs 57.1%; P = 0.004) and older patients [age(median), 57 vs 63.5; P = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups(ORR: 39.8% vs 35.7%; P = 0.656; DCR: 80.7% vs 83.3%; P = 0.716). The median PFS and OS were also not different between the groups(PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). In the safety analysis with severe AEs, the rates of neutropenia(83.0% vs 66.7%; P = 0.044), anorexia(48.9% vs 28.6%; P = 0.029) and diarrhea(13.6% vs 0.0%; P = 0.009) were markedly lower in the mFOLFIRINOX group.CONCLUSION m FOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy. | Huapyong Kang Jung Hyun Jo Hee Seung Lee Moon Jae Chung Seungmin Bang Seung Woo Park Si Young Song Jeong Youp Park | 2018 | World Journal of Gastrointestinal Oncology2018,10,11: | 6 |
| 4 | 5-氟尿嘧啶、亚叶酸钙、伊立替康和奥沙利铂作为一线方案治疗潜在可切除和局部晚期胰腺癌荟萃分析显示文摘目的评价以5-氟尿嘧啶、亚叶酸钙、伊立替康和奥沙利铂(FOLFIRINOX方案)作为一线方案治疗潜在可切除(BRPC)和局部不可切除胰腺癌(LAPC)的有效性。方法符合条件的文献均来自PubMed、Cochrane Library、EMBASE。分析手术切除率和根治性(R0)切除率。数据表示为具有95%可信区间(95%C/)的加权合并比例。结果共纳入14项研究,包含了408例患者。在一线FOLFIRINOX治疗后,手术切除率为42.0%(95%CI:28.0%-56.0%),根治性(R0)切除率为41.0%(95%CI:37.0%~45.0%),中位总生存期范围15.5—35.4个月,中位无进展生存期10—17.8个月。结论作为一线方案,FOLFIRINOX化疗对潜在可切除和局部晚期胰腺癌患者疗效显著,毒副反应可控。 | 徐锡枫 郑松 王珍 钱元 贾长库 | 2018 | 中华肝胆外科杂志2018,24,1: | 6 |
| 5 | Comparison of gemcitabine plus nab-paclitaxel and FOLFIRINOX in metastatic pancreatic cancer显示文摘BACKGROUND Gemcitabine plus nab-paclitaxel(GA)and modified FOLFIRINOX(FFX)have been widely used as standard first-line treatment in pancreatic cancer.However,it is unclear which regimen is more efficacious.AIM To evaluate a retrospective analysis comparing the efficacy and safety of FFX and GA as first-line chemotherapeutic regimens in patients with metastatic pancreatic cancer.METHODS We retrospectively analyzed and compared outcomes in 101 patients who presented with pancreatic cancer and were treated with either GA(n=54)or FFX(n=47).Moreover,we performed subgroup analysis based on the neutrophil/lymphocyte ratio(NLR)and Eastern Cooperative Oncology Group(ECOG)performance status.RESULTS There were no significant differences between two groups in baseline characteristics,except for the ECOG performance status.The median progression-free survival(PFS)(6.43 mo vs 4.90 mo,P=0.058)was comparable between two groups;however,median overall survival(OS)(10.17 mo vs 6.93 mo,P=0.008)was longer in patients who received GA regimen.In patients with ECOG 0(PFS:8.93 mo vs 5.43 mo,P=0.002;OS:16.10 mo vs 6.97 mo,P=0.000)and those with NLR<3(PFS:8.10 mo vs 6.57 mo,P=0.008;OS:12.87 mo vs 9.93 mo,P=0.002),GA regimen showed higher efficacy.CONCLUSION GA regimen may be recommended to the patients with NLR<3 or ECOG 0 status although GA and FFX showed comparable efficacy outcomes in patients with metastatic pancreatic cancer. | Sung Yong Han Dong Uk Kim Young Mi Seol Suk Kim Nam Kyung Lee Seung Baek Hong Hyung-Il Seo | 2020 | World Journal of Clinical Cases2020,8,17: | 5 |
| 6 | FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer显示文摘Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers. | Chiara Caparello Laura L Meijer Ingrid Garajova Alfredo Falcone Tessa Y Le Large Niccola Funel Geert Kazemier Godefridus J Peters Enrico Vasile Elisa Giovannetti | 2016 | World Journal of Gastroenterology2016,22,31: | 4 |
| 7 | The efficacy and safety of modified FOLFIRINOX as first-line chemotherapy for Chinese patients with metastatic pancreatic cancer显示文摘Background: Oxaliplatin, irinotecan, 5-fluorouracil, and l-leucovorin (FOLFIRINOX) has become one of the first-line treatment options for advanced pancreatic cancer (PC). However, the relatively high rate of grade 3 or 4 adverse events associated with the standard dosage of FOLFIRINOX limits its widespread use in clinical practice. In this study, we were to evaluate the efficacy and safety of a modified FOLFIRINOX regimen as a first-line chemotherapy for Chinese patients with metastatic PC. Methods: Patients with histologically confirmed primary metastatic pancreatic adenocarcinoma with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 were recruited to receive the modified FOLFIRINOX regimen (intravenous infusion of oxaliplatin, 65 mg/m2;irinotecan, 150 mg/m2;l-leucovorin, 200 mg/ m2;and 5-fluorouracil, 2400 mg/m2, repeated every 2 weeks). The treatment was continued for 12 cycles unless the patient had progressive disease (PD), stable disease (SD) with symptom deterioration, unacceptable adverse events, or requested to terminate the treatment prematurely. The primary endpoint was objective response rate (ORR). Results: Sixty-five patients were enrolled from July 2012 to April 2017 in three institutions, and they all received at least one cycle of chemotherapy, with a median of 8 cycles (range 1-12 cycles). No complete response was observed. Twenty-one (32.3%) patients had partial responses, and 27 (41.5%) had SD. The ORR and disease control rate of the study cohort was 32.3% and 73.8%. The estimated median overall survival and progression-free survival were 11.60 (95% confidence interval [CI] 8.76-14.44) and 5.77 (95% CI 5.00-6.54) months. Major grade 3 or 4 adverse events included neutropenia (12.3%) and diarrhea (6.2%). No treatment-related death was observed. Conclusions: Modified FOLFIRINOX was well-tolerated and might be a promising option as first-line therapy for Chinese patients with metastatic PC. | Zhi-Qiang Wang Fei Zhang Ting Deng Le Zhang Fen Feng Feng-Hua Wang Wei Wang De-Shen Wang Hui-Yan Luo Rui-Hua Xu Yi Ba Yu-Hong Li | 2019 | Cancer Communications2019,39,1: | 4 |
| 8 | 吉西他滨/白蛋白结合型紫杉醇与FOLFIRINOX用于晚期胰腺癌姑息性一线治疗:倾向评分分析解读显示文摘通过比较真实世界接受FOLFIRINOX(亚叶酸+奥沙利铂+伊立替康+氟尿嘧啶)或GN(吉西他滨+白蛋白结合型紫杉醇)方案治疗的晚期胰腺癌患者的临床结果来指导临床实践。该研究为三中心的回顾性队列研究,采用倾向评分逆概率加权法调整研究组之间的混杂因素。FOLFIRINOX组和GN组的主要研究终点(OS)和次要研究终点(PFS、DCR、ORR)在倾向评分矫正前后差异均无统计学意义。FOLFIRINOX组粒缺性发热和腹泻患者发生比例显著高于GN组,而出现中性粒细胞减少、周围神经病变、胆管炎和疲劳症状的比例两组相近。目前尚不能证明FOLFIRINOX方案和GN方案的疗效差异,在临床实践过程中应考虑患者临床特征选择合适的治疗方案。 | 张娜 王锦毓 应杰儿 | 2022 | 肿瘤学杂志2022,28,2: | 3 |
| 9 | Evolving treatment landscape for early and advanced pancreatic cancer显示文摘Pancreatic ductal adenocarcinoma is an infrequent cancer with a high disease related mortality rate, even in the context of early stage disease. Until recently, the rate of death from pancreatic cancer has remained largely similar whereby gemcitabine monotherapy was the mainstay of systemic treatment for most stages of disease. With the discovery of active multiagent chemotherapy regimens, namely FOLFIRINOX and gemcitabine plus nab-paclitaxel, the treatment landscape of pancreatic cancer is slowly evolving. FOLFIRINOX and gemcitabine plus nab-paclitaxel are now considered standard first line treatment options in metastatic pancreatic cancer. Studies are ongoing to investigate the utility of these same regimens in the adjuvant setting. The potential of these treatments to downstage disease is also being actively examined in the locally advanced context since neoadjuvant approaches may improve resection rates and surgical outcomes. As more emerging data become available, the management of pancreatic cancer is anticipated to change significantly in the coming years. | Sally C Lau Winson Y Cheung | 2017 | World Journal of Gastrointestinal Oncology2017,9,7: | 3 |
| 10 | Multicenter phase Ⅱ trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer显示文摘AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, open-label, phase Ⅱ trial. Patients with unresectable PC, who showed disease progression during GEMbased chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin(RIO; irinotecan 120 mg/m^2 and oxaliplatin 60 mg/m^2), which was set according to the phase Ⅰ study of FOLFIRINOX. The objective response rate(ORR), disease control rate(DCR), progressionfree survival(PFS), overall survival(OS), adverse events were evaluated. Additionally, changes in quality of life(QoL) were assessed using a questionnaire on QoL.RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval(CI): 3.7-7.9] and median OS was 9.0 mo(95%CI: 6.4-11.6). Neutropenia(64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia(16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment(45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities. | Moon Jae Chung Huapyong Kang Ho Gak Kim Jong Jin Hyun Jun Kyu Lee Kwang Hyuck Lee Myung Hwan Noh Dae Hwan Kang Sang Hyub Lee Seungmin Bang 无 | 2018 | World Journal of Gastrointestinal Oncology2018,10,12: | 3 |
| 11 | Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy显示文摘AIM To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic cancer.METHODS This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin(85 mg/m2 in over 120 min) followed by leucovorin(400 mg/m2 in over 120 min), with the addition, after 30 min of irinotecan(180 mg/m2 in over 90 min) then 5 fluorouracil(5FU)(400 mg/m2 administred intravenous bolus), followed by 5FU(2400 mg/m2 intraveinous infusion over 46 h) repeated every 2 wk. Geriatric parameters were recorded at the beginning. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was evaluated by CT scan. Treatment continued until disease progression, unacceptable toxicities or patient refusal.RESULTS Fifty-two patients aged from 70 to 87 years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic cancer. Most of them were in good general condition, 82.7% had a 0-1 performance status and 61.5% had a Charlson Comorbidity Index < 10. The most frequent severe toxicities were neutropenia(17 patients, n = 32.7%) and diarrhea(35 patients n = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4 toxicity. Thirty-nine patients(75%) initially received an adapted dose of chemotherapy. The dosage was adjusted for 26% of patients during the course of treatment. Tumor response evaluated by RECIST criteria showed a controlled disease for 25 patients(48.1%), a stable disease for 13 and a partial response for 12 patients. Time under treatment was higher for colorectal cancer with a median time of 2.44 mo(95%CI: 1.61-3.25). Overall survival was 43.88 mo for colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or multivariate analysis, none of geriatric parameters were linked to overall survival. Only the type of tumor(pancreatic/colorectal) was linked in both analysis.CONCLUSION For people over 70 years old, FOLFIRINOX regimen seems to induce manageable toxicities but similar, even higher, median survival rates compared to younger people. | Jean-Florian Guion-Dusserre Aurélie Bertaut Fran?ois Ghiringhelli Julie Vincent Valérie Quipourt Sophie Marilier Zoé Tharin Leila Bengrine-Lefevre | 2016 | World Journal of Gastroenterology2016,22,42: | 2 |
| 12 | Dilemma of first line regimens in metastatic pancreatic adenocarcinoma显示文摘Pancreatic cancer is one of the deadliest cancers,ranking fourth among cancer-related deaths. Despite all the major molecular advances and treatment breakthroughs, mainly targeted therapies, the cornerstone treatment of metastatic pancreatic cancer(m PC) remains cytotoxic chemotherapy. In 2016, more than 40 years after the introduction of gemcitabine in the management of m PC, the best choice for first-line treatment has not yet been fully elucidated. Two main strategies have been adopted to enhance treatment efficacy. The first strategy is based on combining non-cross resistant drugs, while the second option includes the development of newer generations of chemotherapy. More recently, two new regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel(GNP), have both been shown to improve overall survival in comparison with gemcitabine alone, at the cost of increased toxicity. Therefore, the best choice for first line therapy is a matter of debate. For some authors, FOLFIRINOX should be the first choice in patients with an Eastern Cooperative Oncology Group score(0-1) given its lower hazard ratio. However, others do not share this opinion. In this paper, we review the main comparison points between FOLFIRINOX and GNP. We analyze the two pivotal trials to determine the similarities and differences in study design. In addition, we compare the toxicity profile of the two regimens as well as the impact on quality of life. Finally, we present studies revealing real life experiences and review the advantages and disadvantages of possible second-line therapies including their cost effectiveness. | Marwan Ghosn Tony Ibrahim Tarek Assi Elie El Rassy Hampig Raphael Kourie Joseph Kattan | 2016 | World Journal of Gastroenterology2016,22,46: | 2 |
| 13 | Folfirinox chemotherapy prolongs stent patency in patients with malignant biliary obstruction due to unresectable pancreatic cancer显示文摘Background:Stent insertion for biliary decompression to relieve jaundice and subsequent biliary infection is necessary for patients with biliary obstruction caused by pancreatic cancer,and it is important to keep the stent patent as long as possible.However,few studies have compared stent patency in terms of chemotherapy in patients with pancreatic cancer.This study aimed to evaluate the differences in stent patency in terms of recently evolving chemotherapy.Methods:Between January 2015 and May 2017,161 patients with pancreatic cancer who had undergone biliary stent insertion with a metal stent were retrospectively analyzed.The relationship between chemotherapy and stent patency was assessed.Additionally,overall survival according to the treatment,risk factors for stent patency,and long-term adverse events were evaluated.Results:Median stent patency was 42 days for patients with the best supportive care and 217 days for patients with chemotherapy(conventional gemcitabine-based chemotherapy and folfirinox)(P<0.001).Furthermore,the folfirinox group showed the longest median stent patency and overall survival,with 283 days and 466 days,respectively(P<0.001)despite higher adverse events rate.Patients who underwent folfirinox chemotherapy after stent insertion had better stent patency in multivariate analysis(HR=0.26;95%CI:0.12–0.60;P=0.001).Conclusions:Compared with patients who received best supportive care only,patients who underwent chemotherapy after stent insertion had better stent patency.More prolonged stent patency can be expected for patients with folfirinox than conventional gemcitabine-based chemotherapy. | Jinwoo Kang Sang Hyub Lee Jin Ho Choi Woo Hyun Paik Dong-Won Ahn Ji Bong Jeong Ji Kon Ryu Yong-Tae Kim | 2020 | Hepatobiliary & Pancreatic Diseases International2020,19,6: | 2 |
| 14 | Metastatic pancreatic cancer: Is there a light at the end of the tunnel?显示文摘Due to extremely poor prognosis,pancreatic cancer(PDAC)represents the fourth leading cause of cancerrelated death in Western countries.For more than a decade,gemcitabine(Gem)has been the mainstay of first-line PDAC treatment.Many efforts aimed at improving single-agent Gem efficacy by either combining it with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation provided disappointing results.Recently,the field of systemic therapy of advanced PDAC is finally moving forward.Polychemotherapy has shown promise over single-agent Gem:regimens like PEFG-PEXG-PDXG and GTX provide significant potential advantages in terms of survival and/or disease control,although sometimes at the cost of poor tolerability.The PRODIGE 4/ACCORD 11 was the first phaseⅢtrial to provide unequivocal benefit using the polychemotherapy regimen FOLFIRINOX;however the less favorable safety profile and the characteristics of the enrolled population,restrict the use of FOLFIRINOX to young and fit PDAC patients.The nanoparticle albumin-bound paclitaxel(nab-Paclitaxel)formulation was developed to overcome resistance due to the desmoplastic stroma surrounding pancreatic cancer cells.Regardless of whether or not this is its main mechanisms of action,the combination of nabPaclitaxel plus Gem showed a statistically and clinically significant survival advantage over single agent Gem and significantly improved all the secondary endpoints.Furthermore,recent findings on maintenance therapy are opening up potential new avenues in the treatment of advanced PDAC,particularly in a new era in which highly effective first-line regimens allow patients to experience prolonged disease control.Here,we provide an overview of recent advances in the systemic treatment of advanced PDAC,mostly focusing on recent findings that have set new standards in metastatic disease.Potential avenues for further development in the metastatic setting and current efforts to integratenew effective chemotherapy regimens in earlier stages of disease(neoadjuvant,adjuvant,and multimodal approaches in both resectable and unresectable patients)are also briefly discussed. | Vanja Vaccaro Isabella Sperduti Sabrina Vari Emilio Bria Davide Melisi Carlo Garufi Carmen Nuzzo Aldo Scarpa Giampaolo Tortora Francesco Cognetti Michele Reni Michele Milella | 2015 | World Journal of Gastroenterology2015,21,16: | 2 |
| 15 | 改良FOLFIRINOX方案一线化疗中国转移性胰腺癌患者的疗效与安全性研究显示文摘背景与目的奥沙利铂(oxaliplatin)、伊立替康(irinotecan)、5-氟尿嘧啶(5-fluorouracil)和1-醛氢叶酸(l-leucovorin)联合用药(即FOLFIRINOX方案)已成为晚期胰腺癌(pancreatic cancer,PC)的一线治疗方案之一。然而,与FOLFIRINOX标准剂量相关的3级或4级不良事件的较高发生率限制了该方案在临床上的广泛应用。在本研究中,我们对改良FOLFIRINOX方案一线化疗中国转移性PC患者的疗效和安全性进行了评价。方法将组织学证实为原发转移性胰腺癌,且东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)体能状态评分为0-2的患者纳入本研究。所有患者均接受改良FOLFIRINOX方案治疗(静脉滴注奥沙利铂65 mg/m^2、伊立替康150 mg/m^2、l-醛氢叶酸200 mg/m^2、5-氟尿嘧啶2400 mg/m^2,每2周重复1次)。治疗持续12个周期,除非患者出现疾病进展(progressive disease,PD)、症状恶化的疾病稳定(stable disease,SD)、不可耐受的不良事件或要求提前终止治疗。主要终点为客观缓解率(objective response rate,ORR)。结果2012年7月至2017年4月期间,共有来自3个机构的65例患者被纳入本研究。所有患者均接受了至少1个周期化疗,化疗周期中位数为8个周期(范围:1-12个周期)。本研究中未观察到完全缓解。21(32.3%)例患者为部分缓解,27(41.5%)例表现为SD。总体人群的ORR和疾病控制率(diseasecontrol rate,DCR)分别为32.3%和73.8%。中位总生存期和无进展生存期分别为11.60[95%置信区间(confidence interval,CI):8.76-14.44]个月和5.77(95%CI:5.00-6.54)个月。主要的3级或4级不良事件包括中性粒细胞减少(12.3%)和腹泻(6.2%)。未观察到与治疗相关的死亡。结论改良FOLFIRINOX具有良好的耐受性,可作为中国转移性PC中国患者的一线治疗方案。 | Zhi‑Qiang Wang Fei Zhang Ting Deng Le Zhang Fen Feng Feng‑Hua Wang Wei Wang De‑Shen Wang Hui‑Yan Luo Rui‑Hua Xu Yi Ba Yu‑Hong Li | 2019 | 癌症2019,38,8: | 2 |
| 16 | FOLFIRINOX vs gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study显示文摘BACKGROUND FOLFIRINOX and gemcitabine plus nab-paclitaxel(Gem+nabPTX)were recently introduced for metastatic pancreatic cancer treatment.However,studies that compared these two regimens and studies in Asian populations are lacking.AIM To compare the treatment outcomes of FOLFIRINOX and Gem+nabPTX regimen for metastatic pancreatic cancer treatment in Korean population.METHODS Patients with metastatic or recurrent pancreatic cancer treated with FOLFIRINOX(n=86)or Gem+nabPTX(n=81)as the first-line since January 2015 were identified using the Severance Hospital Pancreatic Cancer Cohort Registry.Treatment efficacy,treatment-related adverse events and economic aspects were compared.RESULTS Patients in the FOLFIRINOX group were significantly younger(54 vs 65 years;P<0.001)and had better performance statuses at diagnosis.The median overall survival(10.7 vs 12.1 mo;P=0.157),progression-free survival(8.0 vs 8.4 mo;P=0.134),and objective response rates(33.7%vs 46.9%;P=0.067)were not significantly different when compared with Gem+nabPTX group.Grade≥3 neutropenia and gastrointestinal adverse events were more common in the FOLFIRINOX group.The drug costs of both regimens were similar.CONCLUSION Treatment efficacy and economic burdens were comparable between the two regimens.But,the details of adverse event were different.Gem+nabPTX regimen might be considered preferentially in certain conditions. | In Rae Cho Huapyong Kang Jung Hyun Jo Hee Seung Lee Moon Jae Chung Jeong Youp Park Seung Woo Park Si Young Song Chansik An Mi-Suk Park Seungmin Bang | 2020 | World Journal of Gastrointestinal Oncology2020,12,2: | 1 |
| 17 | MUC1 promotes glycolysis through inhibiting BRCA1 expression in pancreatic cancer显示文摘Enhanced glucose metabolism is one of the hallmarks of pancreatic cancer. MUC1, a transmembrane protein, is a global regulator of glucose metabolism and essential for progression of pancreatic cancer. To clarify the role of MUC1 in glucose metabolism, we knocked out MUC1 in Capan-1 and CFPAC-1 cells. MUC1 knockout(KO) cells uptook less glucose and secreted less lactate with a much lower proliferating rate. The m RNA level of key enzymes in glycolysis also decreased significantly in MUC1 KO cells.We also observed increased expression of breast cancer type 1 susceptibility protein(BRCA1) in MUC1 KO cells. Since BRCA1 has a strong inhibitory effect on glycolysis, we want to know whether the decreased glucose metabolism in MUC1 KO cells is due to increased BRCA1 expression. We treated wild type(WT) and MUC1 KO cells with BRCA1 inhibitor. BRCA1 inhibition significantly enhanced glucose uptake and lactate secretion in both WT and MUC1 KO cells. Expression of key enzymes in glycolysis also elevated after BRCA1 inhibition. Elevated glucose metabolism is known to facilitate cancer cells to gain chemoresistance. We treated MUC1 KO cells with gemcitabine and FOLFIRINOX in vitro and in vivo. The results showed that MUC1 KO sensitized pancreatic cancer cells to chemotherapy both in vitro and in vivo. In conclusion, we demonstrated that MUC1 promotes glycolysis through inhibiting BRCA1 expression. MUC1 may be a therapeutic target in pancreatic cancer treatment. | FU Xiao TANG Neng XIE Wei-Qi MAO Liang QIU Yu-Dong | 2020 | Chinese Journal of Natural Medicines2020,18,3: | 1 |
| 18 | FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study显示文摘BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy(L1)in advanced pancreatic ductal adenocarcinoma(aPDAC).FOLFOXIRI,a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil,has demonstrated efficacy and feasibility in colorectal cancer.AIM To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.METHODS Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions,with either FOLFOXIRI(n=165)or FOLFIRINOX(n=124)regimens.FOLFOXIRI consisted of irinotecan(165 mg/m2),oxaliplatin(85 mg/m2),leucovorin(200 mg/m2)and 5-fluorouracil(3200 mg/m2 as a 48-h continuous infusion)every 2 wk.Ninety-six pairs of patients were selected through propensity score matching,and clinical outcomes of the two treatment regimens were compared.RESULTS Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts,respectively.After propensity score matching,survival rates remained similar between the two regimens in terms of overall survival(hazard ratio=1.22;P=0.219)and progression-free survival(hazard ratio=1.27;P=0.120).The objective response rate was 37.1%in the FOLFOXIRI group vs 47.8%in the FOLFIRINOX group(P=0.187).Grade 3/4 toxicities occurred in 28.7%of patients in the FOLFOXIRI cohort vs 19.5%in the FOLFIRINOX cohort(P=0.079).FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events.Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5%with both regimens.CONCLUSION FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX.The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors. | Angélique Vienot Hortense Chevalier Clément Bolognini Elisabeta Gherga Elodie Klajer Aurélia Meurisse Marine Jary Stefano Kim Christelle d’Engremont Thierry Nguyen Fabien Calcagno Hamadi Almotlak Francine Fein Meher Nasri Syrine Abdeljaoued Anthony Turpin Christophe Borg Dewi Vernerey | 2020 | World Journal of Gastrointestinal Oncology2020,12,3: | 0 |
| 19 | Real-world evidence on first-and second-line palliative chemotherapy in advanced pancreatic cancer显示文摘In spite of recent diagnostic and therapeutic advances,the prognosis of pancreatic ductal adenocarcinoma(PDAC)remains very poor.As most patients are not amenable to curative intent treatments,optimized palliative management is highly needed.One key question is to what extent promising results produced by randomized controlled trials(RCTs)correspond to clinically meaningful outcomes in patients treated outside the strict frames of a clinical trial.To answer such questions,real-world evidence is necessary.The present paper reviews and discusses the current literature on first-and second-line palliative chemotherapy in PDAC.Notably,a growing number of studies report that the outcomes of the two predominant first-line multidrug regimens,i.e.gemcitabine plus nabpaclitaxel(GnP)and folfirinox(FFX),is similar in RCTs and real-life populations.Outcomes of second-line therapy following failure of first-line regimens are still dismal,and considerable uncertainty of the optimal management remains.Additional RCTs and real-world evidence studies focusing on the optimal treatment sequence,such as FFX followed by GnP or vice versa,are urgently needed.Finally,the review highlights the need for prognostic and predictive biomarkers to inform clinical decision making and enable personalized management in advanced PDAC. | Hakon Blomstrand Atul Batra Winson Y Cheung Nils Oskar Elander | 2021 | World Journal of Clinical Oncology2021,12,9: | 0 |
| 20 | 白蛋白紫杉醇联合吉西他滨与FOLFIRINOX治疗晚期胰腺癌真实世界研究的疗效评价显示文摘1文献来源Chiorean EG,Cheung WY,Giordano G,et al.Real world comparative effectiveness of nab Paclitaxel plus Gemcitabine versus FOLFIRINOX in advanced pancreatic cancer:A systematic review[J].Ther Adv Med Oncol,2019 May 19;11:1758835919850367.doi:10.1177/1758835919850367.2证据水平2a。3背景晚期胰腺癌(advanced pancreatic cancer,aPC)的治疗效果不佳,5年生存率约为3%。单药吉西他滨是aPC的标准治疗方案,但已证实疗效不如联合化疗方案如白蛋白紫杉醇联合吉西他滨(nab Paclitaxel/Gemcitabine,nab P/G)与FOLFIRINOX(氟尿嘧啶+亚叶酸钙+奥沙利铂+伊立替康)。社区治疗中肿瘤科医师对瘦弱的转移性胰腺癌(metastasis pancreatic cancer,mPC)患者倾向于选用nab P/G作为一线治疗,而对年轻男性患者倾向于选用FOLFIRINOX。然而,选择nab P/G或FOLFIRINOX的依据尚不清楚。 | 江志敏(评价) 谢德荣(评价) 赖晓嵘(文献合成) | 2019 | 循证医学2019,19,5: | 0 |