一例FOLFIRINOX方案转化治疗后胰腺癌进展患者的手术治疗与疗效评估

胰腺癌是一种治疗难度较大的恶性肿瘤,目前仍以手术治疗为主。在临床上对于交界可切除及不可切除的胰腺癌患者,在体能状态良好时,多采用FOLFIRINOX化疗方案进行转化治疗,再择期行手术治疗,可取得较好预后。杭州市第一人民医院收治了一例交界可切除的胰腺癌患者,在术前实施为期3个月的FOLFIRINOX治疗,因化疗效果不佳,患者疾病进展,肿瘤侵犯周围血管,经多学科讨论后,研究团队对患者进行了根治性胰十二指肠切除术治疗,术后患者癌胚抗原(CEA)与糖类抗原(CA)199水平持续下降,取得较为良好的生物学效果。术后患者因肾功能衰竭,低蛋白血症无法纠正死亡。研究团队总结认为,FOLFIRINOX化疗方案存在个体差异,其是否能有效进行转化取决于胰腺肿瘤细胞CES2的表达。在临床上常规选择的化疗方案无法取得收益时,可通过PTC药敏实验检测来指导后续的治疗决策,制定患者个体化的精准治疗方案。

FOLFIRINOX方案与吉西他滨方案治疗局限性晚期胰腺癌疗效的对比研究

目的:评估FOLFIRINOX方案与吉西他滨方案治疗局限性晚期胰腺癌(LAPC)患者的生存结果和副作用对比。方法:本研究共纳入129例进行FOLFIRINOX方案化疗和116例吉西他滨方案化疗的患者,比较两组患者总生存期(OS)、无进展生存期(PFS)以及治疗相关副作用和独立危险因素。结果:在129例接受了FOLFIRINOX系统化疗方案的LAPC患者中,中位OS为21.1个月,PFS为15.6个月;而吉西他滨方案组患者的中位OS为18.2个月,PFS为11.3个月。FOLFIRINOX组患者的总生存与吉西他滨组无统计学差异(P=0.167),但较吉西他滨组的无进展生存率高(P=0.005)。其中67.0%的患者同时完成了化疗和化疗后的放疗治疗,无一例因化疗而致死亡,45.7%的患者存在不同程度的化疗不良反应。肿瘤位置对预后有显著影响,肿瘤大小可影响LAPC患者总生存,但FOLFIRINOX化疗方案是LAPC患者无进展生存的独立危险因素。结论:FOLFIRINOX方案是LAPC患者治疗的有效手段,可提高无进展生存时间,且副作用与吉西他滨化疗方案相当。

FOLFIRINOX方案一线治疗转移性胰腺癌临床疗效观察

目的观察FOLFIRINOX方案一线治疗晚期胰腺癌的临床疗效及毒副反应。方法2011年11月至2015年1月,对江苏省肿瘤医院收治的转移性胰腺癌患者12例给予FOLFIRINOX方案一线治疗,2个周期化疗后影像学及实验室检查评价疗效,并观察毒副反应。结果 12例患者中8例PR,4例SD,无PD。疾病控制率100%。达到临床受益反应标准的共8例(67%)。6例患者CA199下降大于30%。12例患者均未出现致死性毒副反应。结论 FOLFIRINOX方案一线治疗晚期胰腺癌的临床疗效好,毒副反应可耐受,改良的FOLFIRINOX方案结合外科手术可能成为今后胰腺癌治疗的新方向。

FOLFIRINOX方案联合载药微球介入灌注化疗栓塞治疗胰腺癌肝转移1例

胰腺癌很难早期发现,多数患者发现时已属晚期,失去了根治性手术的机会。在晚期胰腺癌的治疗中,FOLFIRINOX方案是一线化疗方案中的推荐方案。但是,此方案仍只能将患者的中位生存时间延长到接近一年。寻找可能的新方案或优化现有方案仍然是临床工作中的重要目标。载药微球是血管介入治疗中常用的栓塞材料,通过血管介入的方式进入瘤体中,在阻塞血管的同时缓慢释放治疗药物,已证实在全身多处肿瘤的治疗中有效且不良反应较低。

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

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。

鼓舞人心，但不应盲目乐观——评FOLFIRINOX方案新辅助化疗在可能切除胰腺癌中的应用

1文献来源研究一:Janssen QP,Buettner S,Suker M,et al.Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer:A systematic review and patient level meta analysis[J].J Natl Cancer Inst,2019,111(8):782-794.研究二:Katz MH,Shi Q,Ahmad SA,et al.Preoperative modified FOLFIRINOX treatment followed by Capecitabine based chemoradiation for borderline resectable pancreatic cancer:Alliance for clinical trials in oncology trial A021101[J].JAMA Surg,2016,151(8):e161137.2证据水平1b。

改良FOLFIRINOX与吉西他滨为基础的化疗方案在进展期胰腺癌治疗中的对比研究

目的对比吉西他滨(gemcitabine,G)为基础的一线化疗方案及改良FOLFIRINOX(modified FOLFIRINOX,m FOLFIRINOX)方案治疗不可切除进展期胰腺癌的疗效性及安全性。方法回顾性收集接受指南一级推荐化疗方案治疗的不可切除进展期胰腺癌患者70例。其中,37例接受吉西他滨单药、吉西他滨加替吉奥(gemcitabine plus S-1,GS)或吉西他滨加白蛋白紫杉醇一线化疗(A组),33例接受m FOLFIRINOX方案一线化疗(B组)。m FOLFIRINOX方案奥沙利铂和伊立替康分别减至70 mg/m2和145 mg/m2,其余药物剂量和用法不变。设定主要研究终点为总生存期(overall survival,OS)、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)、3/4级不良反应事件发生率。结果 A组和B组患者中位OS(8.3个月vs 13.5个月),中位PFS(4.3个月vs 6.1个月),两组比较差异均具有统计学意义(均P<0.05)。62例完成临床评效,两组ORR分别为16.2%和36.4%(P>0.05)。A组最常见3/4级不良反应为中性粒细胞减少(16.2%)、发热性感染(10.8%)、血小板减少(8.1%)、过敏反应(8.1%)及腹泻(8.1%);B组为中性粒细胞减少(12.1%)、周围神经病变(9.1%)及腹泻(9.1%)。结论对于不可切除的进展期胰腺癌患者,相较于吉西他滨为基础的一线化疗方案,使用m FOLFIRINOX生存获益更佳且耐受性相当。

改良FOLFIRINOX方案治疗进展期胰腺癌的疗效及安全性

目的探讨改良FOLFIRINOX方案治疗进展期胰腺癌的疗效及安全性。方法前瞻性收集2014年1月至2016年11月接受改良FOLFIRINOX方案化疗的不可切除进展期胰腺癌患者26例。改良FOLFIRINOX方案如下:奥沙利铂70 mg/m^2静滴d1,伊立替康145 mg/m^2静滴d1,亚叶酸钙400 mg/m^2静滴d1,氟尿嘧啶400 mg/m^2静注d1,之后46 h持续静脉输注氟尿嘧啶2400 mg/m^2,14天为1个周期。观察有效率(RR)、总生存时间(OS)、无进展生存时间(PFS)和3、4级不良反应。结果 23例患者可评价疗效,获PR 10例、SD 6例、PD 7例,RR为43. 5%。23例患者的中位OS为16. 6个月(95%CI:7. 6～25. 6个月),中位PFS为8. 9个月(95%CI:3. 3～14. 5个月)。6、12个月生存率分别为82. 6%和47. 1%。8例局部进展期胰腺癌患者的中位OS未达,中位PFS为9. 5个月; 15例转移性胰腺癌患者的中位OS和中位PFS分别为11. 5个月(95%CI:1. 6～21. 3个月)和7. 7个月(95%CI:2. 1～13. 2个月)。共10例患者发生3、4级化疗相关不良事件,以中性粒细胞减少(17. 4%)、周围神经病变(13. 0%)和腹泻(13. 0%)为主,未发生化疗相关性死亡。结论改良FOLFIRINOX方案治疗进展期胰腺癌疗效可观且耐受性较好。

FOLFIRINOX方案与AG方案一线治疗晚期胰腺癌多中心观察性研究

目的开展FOLFIRINOX方案和AG方案一线治疗晚期胰腺癌的多中心观察性研究,总结经验指导临床实践。方法选取2016年1月~2020年6月,在广东省人民医院、中山大学孙逸仙纪念医院、中山大学附属第一院、广东药科大学附属第一医院以及中山市人民医院住院治疗的病理确诊的晚期胰腺癌患者,一线接受FOLFIRINOX方案或AG方案治疗,有完整生存资料。末次随访时间为2020年10月31日。主要终点指标为OS。生存资料检验采用K-M法,以P≤0.05为有统计学意义。结果五个中心共纳入符合纳入标准和排除标准病例62例,按一线化疗方案分为FOLFIRINOX方案组26例和AG方案组36例,FOLFIRINOX方案组与AG方案组中位OS分别为13个月和11个月(P=0.202)、PFS分别为10个月和11个月(P=0.132),两组差别均无统计学意义。一线FOLFIRINOX方案序贯二线AG方案化疗5例,反之有6例,中位OS分别为13个月和11个月。CA199高于正常值59倍或以上,AG组OS中位数10.21个月,数值上似长于FOLFIRINOX组的3.5个月。客观有效率、不良反应等缺漏较多,放弃统计分析。结论FOLFIRINOX方案和AG方案一线治疗晚期胰腺癌疗效相似;用药顺序似不影响疗效;CA199水平用于预测不同方案的疗效可能有一定帮助,值得进一步探讨。

Metastasized pancreatic carcinoma with neoadjuvant FOLFIRINOX therapy and R0 resection

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.

吉西他滨联合S-1与FOLFIRINOX方案在进展期胰腺癌治疗中的疗效及安全性比较

目的比较吉西他滨(GEM)联合替吉奥(S-1)与FOLFIRINOX方案治疗进展期胰腺癌的临床疗效、安全性及生存情况。方法将80例进展期胰腺癌患者随机分为GS组(42例)及FOLFIRINOX组(38例),其中GS治疗组予吉西他滨联合替吉奥(GEM+S-1,GS)治疗,FOLFIRINOX治疗组予奥沙利铂、伊立替康、注射用氟尿嘧啶(5-FU)、甲酰四氢叶酸钙(LV)治疗,比较两组临床疗效、总生存期(OS)、无进展生存期(PFS)、不良反应发生情况及停药率。结果GS组客观缓解率(ORR)、疾病控制率(DCR)明显高于FOLFIRINOX组(均P<0.05);GS组中位OS为13个月,明显高于FOLFIRINOX组的11个月(P<0.05);GS组无进展生存期为9个月,FOLFIRINOX组为6个月,两组差异无统计学意义(P>0.05);GS组患者白细胞下降、贫血等不良反应总发生率均明显低于FOLFIRINOX组(P<0.05);且GS组停药率明显低于FOLFIRINOX组(P<0.05)。结论吉西他滨联合S-1治疗进展期胰腺癌的的临床疗效和无进展生存期与FOLFIRINOX相似,但吉西他滨联合S-1的总生存期明显高于FOLFIRINOX,对进展期胰腺癌患者的预后有益,吉西他滨联合S-1在治疗过程中不良反应发生率及停药率明显低于FOLFIRINOX,具有更高的安全性,患者耐受度也更好。

FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer

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.

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer

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.

Comparison of gemcitabine plus nab-paclitaxel and FOLFIRINOX in metastatic pancreatic cancer

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.

Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy

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.

Multicenter phase Ⅱ trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer

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.

Folfirinox chemotherapy prolongs stent patency in patients with malignant biliary obstruction due to unresectable pancreatic cancer

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.

Modified FOLFIRINOX for resected pancreatic cancer: Opportunities and challenges

Pancreatic cancer is one of the leading causes of cancer death worldwide.Adjuvant chemotherapy has been developed based on the experiences made with palliative chemotherapy, and advocated to improve long-term survival of patients with this disease. However, the optimal chemotherapeutic regimen remains controversial. Recently, Conroy et al demonstrated the impressive benefits of modified FOLFIRINOX over gemcitabine alone in the multicenter Partenariat de Recherche en Oncologie Digestive 24(PRODIGE-24) trial. The remarkable results mark a new milestone in treating resectable pancreatic cancer and have now changed the standard of care for this patient population. In this commentary, we discuss an issue of difference of tumor grade between the PRODIGE-24 trial and previous phase III trials. We also discuss potential biomarkers predicting therapeutic response to modified FOLFIRINOX. Finally,we summarize several ongoing clinical trials of replacing part of the FOLFIRINOX regimen with Xeloda/S-1/nanoliposomal irinotecan for pancreatic cancer.

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

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。

FOLFIRINOX vs gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study

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.