Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. Impact of preoperative chemoradiotherapy on survival in patients with resectable pancreatic cancer. A reappraisal of preoperative chemoradiation for localized pancreatic head ductal adenocarcinoma in a 5-year single-institution experience Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. A comparative study of neoadjuvant treatment with gemcitabine plus nab-paclitaxel versus surgery first for pancreatic adenocarcinoma. Neoadjuvant Therapy is Associated with a Reduced Lymph Node Ratio in Patients with Potentially Resectable Pancreatic Cancer FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel for Neoadjuvant Treatment of Resectable and Borderline Resectable Pancreatic Head Adenocarcinoma Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study) FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer
Objective : This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC . Summary Background Data : Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer ( BRPC ) , no high-level evidence exists to support the role of such treatment . Methods : This phase 2/3 multicenter r and omized controlled trial was design ed to enroll 110 patients with BRPC who were r and omly assigned to gemcitabine-based neoadjuvant chemoradiation treatment ( 54 Gray external beam radiation ) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea . The primary endpoint was the 2-year survival rate ( 2-YSR ) . Interim analysis was planned at the time of 50 % case enrollment . Results : After excluding the patients who withdrew consent ( n = 8) from the 58 enrolled patients , 27 patients were allocated to neoadjuvant treatment and 23 to upfront surgery groups . The overall 2-YSR was 34.0 % with a median survival of 16 months . In the intention-to-treat analysis , the 2-YSR and median survival were significantly better in the neoadjuvant chemoradiation than the upfront surgery group [ 40.7 % , 21 months vs 26.1 % , 12 months , hazard ratio 1.495 ( 95 % confidence interval 0.66–3.36 ) , P = 0.028 ] . R0 resection rate was also significantly higher in the neoadjuvant chemoradiation group than upfront surgery ( n = 14 , 51.8 % vs n = 6 , 26.1 % , P = 0.004 ) . The safety monitoring committee decided on early termination of the study on the basis of the statistical significance of neoadjuvant treatment efficacy . Conclusion : This is the first prospect i ve r and omized controlled trial on the oncological benefits of neoadjuvant treatment in BRPC . Compared to upfront surgery , neoadjuvant chemoradiation provides oncological benefits in patients with BRPC Background In nonr and omized trials , neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer . As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a r and omized phase II trial . Radiological staging defining resectability was basic information prior to r and omization in contrast to adjuvant therapy trials resting on pathological staging . Patients and methods Patients with resectable adenocarcinoma of the pancreatic head were r and omized to primary surgery ( Arm A ) or neoadjuvant chemoradiotherapy followed by surgery ( Arm B ) , which was followed by adjuvant chemotherapy  in both arms . A total of 254 patients were required to detect a 4.33-month improvement in median overall survival ( mOS ) . Results The trial was stopped after 73 patients ; 66 patients were eligible for analysis . Twenty nine of 33 allocated patients received chemoradiotherapy . Radiotherapy was completed in all patients . Chemotherapy was changed in 3 patients due to toxicity . Tumor resection was performed in 23 vs. 19 patients ( A vs. B ) . The R0 resection rate was 48 % ( A ) and 52 % ( B , P = 0.81 ) and (y)pN0 was 30 % ( A ) vs. 39 % ( B , P = 0.44 ) , respectively . Postoperative complications were comparable in both groups . mOS was 14.4 vs. 17.4 months ( A vs. B ; intention-to-treat analysis ; P = 0.96 ) . After tumor resection , mOS was 18.9 vs. 25.0 months ( A vs. B ; P = 0.79 ) . Conclusion This worldwide first r and omized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity , perioperative morbidity , and mortality . Nevertheless , the trial was terminated early due to slow recruiting and the results were not significant . IS RCT N78805636 ; NCT00335543.ZusammenfassungHintergrundMehrere nichtr and omisierte Studien zeigten , dass eine neoadjuvante Therapie das Überleben bei Patienten mit Pankreaskarzinom verlängert . Beim lokal fortgeschrittenen Rektumkarzinom gehört die neoadjuvante Radiochemotherapie bereits zum Therapiest and ard . Analog wurde der Stellenwert einer Radiochemotherapie beim Pankreaskarzinom in einer r and omisierten Phase-II-Studie untersucht . Das prätherapeutische radiologische Staging war Grundlage dieser Studie i m Gegensatz zu adjuvanten Therapiestudien , die auf pathohistologischem Staging basieren . Patienten und Method enPatienten mit resektablem Pankreaskopfkarzinom wurden r and omisiert in primäre Operation ( Arm A ) versus neoadjuvante Radiochemotherapie gefolgt von einer Operation ( Arm B ) . Beide Gruppen erhielten eine adjuvante Chemotherapie . Es waren 254 Patienten erforderlich , um eine Verbesserung des medianen Gesamtüberlebens von 4,33 Monaten zu erfassen . ErgebnisseDie Studie wurde wegen zögerlicher Rekrutierung nach Einschluss von 73 Patienten beendet . Insgesamt konnten 66 Patienten ausgewertet werden . Die ihnen zugeordnete Radiochemotherapie erhielten 29 von 33 Patienten . Alle Patienten bekamen die vollständige Bestrahlungstherapie . Wegen der Toxizität wurde bei 3 Patienten die Chemotherapie reduziert . Eine Pankreastumorresektion erhielten 23 vs. 19 Patienten ( A vs. B ) . Die R0-Resektionsrate betrug 48 % ( A ) und 52 % ( B , P = 0,81 ) . Bei 30 % ( A ) versus 39 % ( B , P = 0,44 ) der resezierten Patienten waren keine Lymphknotenmetastasen vorh and en . Die postoperativen Komplikationen waren in beiden Gruppen vergleichbar . Das mediane Gesamtüberleben betrug 14,4 vs. 17,4 Monate ( A vs. B ; „ Intention-to-treat“-Analyse ; P = 0,96 ) . Nach Pankreastumorresektion stieg das Gesamtüberleben auf 18,9 vs. 25,0 Monate ( A vs. B ; P = 0,79).SchlussfolgerungDiese weltweit erste r and omisierte Studie zur neoadjuvanten Radiochemotherapie beim Pankreaskopfkarzinom war in Bezug auf Toxizität sowie perioperative Morbidität und Mortalität gut durchführbar . Die Ergebnisse sind jedoch nicht signifikant , da diese r and omisierte Studie vorzeitig wegen mangelnder Rekrutierung beendet werden musste . IS RCT N78805636 ; NCT00335543 PURPOSE We conducted a phase II trial to assess the outcomes of patients who received preoperative gemcitabine-based chemoradiation and pancreaticoduodenectomy ( PD ) for stage I/II pancreatic adenocarcinoma . PATIENTS AND METHODS Eligible patients with pancreatic head/uncinate process adenocarcinoma and radiographically defined potentially resectable disease received chemoradiation with 7 weekly intravenous ( IV ) infusions of gemcitabine ( 400 mg/m(2 ) IV over 30 minutes ) plus radiation therapy ( 30 Gy in 10 fractions over 2 weeks ) . Patients underwent restaging 4 to 6 weeks after completion of chemoradiation and , in the absence of disease progression , were taken to surgery . RESULTS The study enrolled 86 patients . At the time of restaging , disease progression or a decline in performance status precluded 13 patients from surgery . Seventy-three ( 85 % ) of 86 patients were taken to surgery , extrapancreatic disease was found in nine , and 64 ( 74 % ) of 86 underwent a successful PD . Median overall survival ( 86 patients ) was 22.7 months with a 27 % 5-year survival . Median survival was 34 months for the 64 patients who underwent PD and 7 months for the 22 unresected patients ( P < .001 ) . The 5-year survival for those who did and did not undergo PD was 36 % and 0 % , respectively . CONCLUSION Preoperative gemcitabine-based chemoradiation followed by restaging and evaluation for surgery separated the study population into two different subsets : patients likely to benefit from PD ( n = 64 ) and those in whom surgery would be unlikely to provide clinical benefit ( n = 22 ) . Furthermore , the encouraging overall survival observed in this large trial supports the continued investigation of gemcitabine-based preoperative therapy in resectable pancreatic cancer AIM To explore whether preoperative chemoradiation therapy improves survival of patients with pancreatic cancer undergoing resectional surgery .  METHODS Forty-seven patients with a malignant pancreatic tumor localized in the head or uncinate process of the pancreas underwent radical pancreatico-duodenectomy .  Twenty-two received chemoradiation therapy ( gemcitabine and radiation dose 50.4 Gy ) before surgery ( CRR ) and 25 patients underwent surgery only ( RO ) . The study was non-r and omised . Patients were identified from a prospect i ve data base . RESULTS The median survival time was 30.2 mo in the CRR group and 35.9 mo in the RO group . No statistically significant differences were found in subclasses according to lymph node involvement , TNM stages , tumor size , or perineural invasion . The one , three and five year survival rates were 81 % , 33 % and 33 % , respectively , in the CRR group and 72 % , 47 % and 23 % , respectively , in the RO group . In ductal adenocarcinoma , the median survival time was 27 mo in the CRR group and 20 mo in the RO group . No statistically significant differences were found in the above subclasses . The one , three and five year survival rates were 79 % , 21 % and 21 % , respectively , in the CRR group and 64 % , 50 % and 14 % , respectively , in the RO group . The overall hospital mortality rate was 2 % . The morbidity rate was 45 % in the CRR group and 32 % ( NS ) in the RO group . CONCLUSION Major multicenter r and omized studies are needed to conclusively assess the impact of neoadjuvant treatment in the management of pancreatic cancer Resection of localized pancreatic head ductal adenocarcinoma ( LPHDA ) has a limited impact on survival . Mechanisms of improvement provided by preoperative chemoradiation therapy ( CRT ) remain under debate . This study analyzes the outcome of patients treated for LPHDA to delineate the benefits of CRT . Among 87 patients with LPHDA , 17 had a pancreaticoduodenectomy alone ( group I ) . Thirtynine with initially resectable cancers received CRT with 5-fluorouracil-based chemotherapy ( group II ) . Thirty-one with initially unresectable cancers were similarly treated by CRT ( group III ) . Patients in groups II and III were restaged after completion of CRT . In patients with resectable disease , resection was planned . Patients in groups I and II were statistically comparable in terms of age , sex , and pretherapeutic stage . Median survival and 2-year overall survival in group I were 13.7 months and 31 % , respectively . In group II , 23 patients ( 59 % ) had a pancreaticoduodenectomy ( group IIa ) and 16 patients ( 41 % ) did not have resection ( group IIb ) . Median survival and 2-year overall survival were as follows : group IIa , 26.6 months and 51 % ; and group IIb , 6.1 months and 0 % , respectively . In group IIa , pathologic examination revealed eight major responses ( 35 % ) including two sterilized specimens , and none of the patients had locoregional recurrence . In group III , none of the patients had resection , and median survival was 8 months with one 2-year survivor . Patient selection appears to play a major role with regard to results achieved with preoperative CRT followed by pancreaticoduodenectomy . However , a high histologic response rate and excellent local control can also be achieved IMPORTANCE The prognosis for patients with pancreatic cancer is poor , even after resection with curative intent . Gemcitabine-based chemotherapy is st and ard treatment for advanced pancreatic cancer , but its effect on survival in the adjuvant setting has not been demonstrated . OBJECTIVE To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival . DESIGN , SETTING , AND PATIENTS CONKO-001 ( Charité Onkologie 001 ) , a multicenter , open-label , phase 3 r and omized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection . Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria . Follow-up ended in September 2012 . INTERVENTIONS After stratification for tumor stage , nodal status , and resection status , patients were r and omly assigned to either adjuvant gemcitabine treatment ( 1g/m2 d 1 , 8 , 15 , q 4 weeks ) for 6 months or to observation alone . MAIN OUTCOMES AND MEASURES The primary end point was disease-free survival . Secondary end points included treatment safety and overall survival , with overall survival defined as the time from date of r and omization to death . Patients lost to follow-up were censored on the date of their last follow-up . RESULTS A total of 368 patients were r and omized , and 354 were eligible for intention-to-treat- analysis . By September 2012 , 308 patients ( 87.0 % [ 95 % CI , 83.1%-90.1 % ] ) had relapsed and 316 patients ( 89.3 % [ 95 % CI , 85.6%-92.1 % ] ) had died . The median follow-up time was 136 months . The median disease-free survival was 13.4 ( 95 % CI , 11.6 - 15.3 ) months in the treatment group compared with 6.7 ( 95 % CI , 6.0 - 7.5 ) months in the observation group ( hazard ratio , 0.55 [ 95 % CI , 0.44 - 0.69 ] ; P < .001 ) . Patients r and omized to adjuvant gemcitabine treatment had prolonged overall survival compared with those r and omized to observation alone ( hazard ratio , 0.76 [ 95 % CI , 0.61 - 0.95 ] ; P = .01 ) , with 5-year overall survival of 20.7 % ( 95 % CI , 14.7%-26.6 % ) vs 10.4 % ( 95 % CI , 5.9%-15.0 % ) , respectively , and 10-year overall survival of 12.2 % ( 95 % CI , 7.3%-17.2 % ) vs 7.7 % ( 95 % CI , 3.6%-11.8 % ) . CONCLUSIONS AND RELEVANCE Among patients with macroscopic complete removal of pancreatic cancer , the use of adjuvant gemcitabine for 6 months compared with observation alone result ed in increased overall survival as well as disease-free survival . These findings provide strong support for the use of gemcitabine in this setting . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N34802808 PURPOSE We conducted a phase II trial of preoperative gemcitabine and cisplatin chemotherapy in addition to chemoradiation ( Gem-Cis-XRT ) and pancreaticoduodenectomy ( PD ) for patients with stage I/II pancreatic adenocarcinoma . PATIENTS AND METHODS Chemotherapy consisted of gemcitabine ( 750 mg/m(2 ) ) and cisplatin ( 30 mg/m(2 ) ) given every 2 weeks for four doses . Chemoradiation consisted of four weekly infusions of gemcitabine ( 400 mg/m(2 ) ) combined with radiation therapy ( 30 Gy in 10 fractions administered over 2 weeks ) delivered 5 days per week . Patients underwent restaging 4 to 6 weeks after completion of chemoradiation and , in the absence of disease progression , were taken to surgery . RESULTS The study enrolled 90 patients ; 79 patients ( 88 % ) completed chemo-chemoradiation . Sixty-two ( 78 % ) of 79 patients were taken to surgery and 52 ( 66 % ) of 79 underwent PD . The median overall survival of all 90 patients was 17.4 months . Median survival for the 79 patients who completed chemo-chemoradiation was 18.7 months , with a median survival of 31 months for the 52 patients who underwent PD and 10.5 months for the 27 patients who did not undergo surgical resection of their primary tumor ( P < .001 ) . CONCLUSION Preoperative Gem-Cis-XRT did not improve survival beyond that achieved with preoperative gemcitabine-based chemoradiation ( Gem-XRT ) alone . The longer preoperative interval required more durable biliary decompression ( metal stents ) but was not associated with local tumor progression . The gemcitabine-based chemoradiation platform is a reasonable foundation on which to build future phase II multimodality trials for stage I/II pancreatic cancer incorporating emerging systemic therapies INTRODUCTION Neoadjuvant treatment has been reported to prolong survival in patients with potentially resectable pancreatic adenocarcinoma ( PA ) . However , there are currently limited clinical results available using nab-paclitaxel and gemcitabine in PA . This paper compares the oncological results of patients affected by potentially resectable PA who underwent surgery first ( SF ) versus surgery following neoadjuvant treatment ( NAT ) .  METHODS This is an observational , comparative study whereby data were abstract ed from a prospect i ve data base of patients affected by PA from 2007 to 2016 . RESULTS We included a total of 81 patients ( 36 SF and 45 NAT ) which result ed in being preoperatively similar . Among the NAT patients , treatment was well tolerated and the resection rate was 68.8 % ( 31/45 patients ) . There was a trend towards a higher R1 resection rate in the SF group compared with the NAT ( 13.8 % vs 3.2 % ; p = 0.1 ) . Median overall survival in the resected NAT group was higher ( 30.6 vs 22.1 months ; p = 0.04 ) . In the borderline resectable group , overall survival was found to be four times higher compared with SF ( 43.6 versus 13.5 months ; p = 0.001 ) . CONCLUSIONS These data suggest that neoadjuvant treatment with gemcitabine/nab-paclitaxel is a safe and effective option for potentially resectable PA compared with the SF approach Abstract Background The use of neoadjuvant therapy ( NAC ) for the treatment of potentially resectable pancreatic cancer remains controversial . In this study , we sought to evaluate cancer-specific endpoints in patients undergoing a NAC versus a surgery-first ( SF ) approach with specific emphasis on lymph node metastases . Methods A total of 222 patients who underwent NAC and 85 patients who underwent SF were identified from 1990 to 2008 and compared for cancer-related endpoints . Peripancreatic lymph nodes from 135 neoadjuvant therapy patients were evaluated for histologic tumor regression . Results Patients who underwent NAC followed by surgery had improved overall survival and time to local recurrence compared with the SF approach . NAC patients were less likely to have lymph node metastases ( p = 0.001 ) , lymphovascular invasion ( LVI ) , and had smaller tumors . On multivariate analysis , lymph node positivity was associated with SF , tumor size , and the presence of LVI . NAC patients with N0 disease had equivalent outcomes to patients with a low-LNR ( 0.01–0.15 ) , whereas patients with a LNR > 0.15 had reduced survival , and time to local and distant recurrence . Ten of 135 ( 7.4 % ) NAC patients had evidence of tumor regression in at least one lymph node . Conclusions Patients with potentially resectable PDAC selected to undergo NAC  had improved survival and longer time to recurrence . Although some of these differences may be related to improvements in multimodality therapy completion rates , tumor regression in lymph node metastases exists and may demonstrate a biologic benefit of NAC compared with a SF approach Background Both FOLFIRINOX and gemcitabine/nab-paclitaxel ( G-nP ) are used increasingly in the neoadjuvant treatment ( NAT ) of pancreatic ductal adenocarcinoma ( PDA ) . This study aim ed to compare neoadjuvant FOLFIRINOX and G-nP in the treatment of resectable ( R ) and borderline resectable ( BR ) head PDA . Methods A single-institution retrospective review of R and BR patients undergoing pancreaticoduodenectomy after NAT with FOLFIRINOX or G-nP was performed . Comparative analysis was performed using inverse-probability-weighted ( IPW ) estimators . The end points of the study were overall survival ( OS ) and an 80 % reduction in CA19 - 9 with NAT . Results In this study , 193 patients were analyzed , with 73 patients receiving FOLFIRINOX and 120 patients receiving G-nP.  The median OS was 38.7 months for FOLFIRINOX versus 28.6 months for G-nP ( p = 0.214 ) . The patients who received FOLFIRINOX were younger and had fewer comorbidities , more BR disease , and larger tumors than those treated with G-nP ( all p < 0.05 ) . The two regimens were equally effective in achieving an 80 % decline in CA19 - 9 ( p = 0.8 ) . The R0 resection rates were similar ( 80 % ) , but FOLFIRINOX was associated with a reduction in pN1 disease ( 56 % vs. 72 % ; p = 0.028 ) . The receipt of adjuvant therapy was similar ( 74 vs. 75 % ; p = 0.79 ) . In the Cox regression analysis with adjustment for baseline and treatment-related variables ( FOLFIRINOX vs. G-nP , age , gender , computed tomography ( CT ) tumor size , BR vs. R , pre-NAT CA19 - 9 ) , regimen type was not associated with a survival benefit . In the IPW analysis of 166 patients , however , the average treatment effect of FOLFIRINOX was to increase OS by 4.9 months compared with G-nP ( p = 0.012 ) . Conclusions Both FOLFIRINOX and G-nP are viable options for neoadjuvant treatment of PDA . In this study , neoadjuvant FOLFIRINOX was associated with a 4.9-month improvement in survival compared with G-nP after adjustment for covariates Background At time of diagnosis , less than 10 % of patients with pancreatic adenocarcinomas ( PDAC ) are considered to be immediately operable ( i.e. resectable ) . Considering their poor overall survival ( OS ) , only tumours without vascular invasion ( NCCN 2017 ) should be considered for resection , i.e. those for which resection with disease-free margins ( R0 ) is theoretically possible in absence of presurgery treatment . With regard to high R1 rates and undetectable locoregional and /or metastatic spreading prior to surgery explain ( at least in part ) the observed 1-year relapse and mortality rates of 50 and 25 % , respectively . Today , upfront surgery followed by adjuvant chemotherapy is the reference treatment in Europe . The main limitation of the adjuvant approach is the low rate of completion of the full therapeutic sequence . Indeed , only 47 to 60 % patients received any adjuvant therapy after resection compared to more than 75 % for neoadjuvant therapy . No previous prospect i ve study has compared this approach to a neoadjuvant FOLFIRINOX or FOLFOX chemotherapy for resectable PDAC . Methods PANACHE01-PRODIGE48 is a prospect i ve multicentre controlled r and omized non comparative Phase II trial , evaluating the safety and efficacy of two regimens of neo-adjuvant chemotherapy ( 4 cycles of mFOLFIRINOX or FOLFOX ) relative to the current reference treatment ( surgery and then adjuvant chemotherapy ) in patients with resectable PDAC . The main co- primary endpoints are OS rate at 12 months and the rate of patients undergoing the full therapeutic sequence . Discussion The “ ideal ” cancer treatment for resectable PDAC would have the following characteristics : administration to the highest possible proportion of patients , ability to identify fast-progressing patients ( i.e. poor c and i date s for surgery ) , a low rate of R1 resections ( through optimisation of local disease control ) , and an acceptable toxicity profile . The neoadjuvant approach may meet all these criteria . With respect to published data on the efficacy of FOLFOX and mFOLFIRINOX , these two regimens are potential c and i date s for neoadjuvant use in the aim to optimising oncological outcomes in resectable PDAC.Trial registration Clinical Trials.gov , NCT02959879 . Trial registration date : November 9 , 2016 BACKGROUND Among patients with metastatic pancreatic cancer , combination chemotherapy with fluorouracil , leucovorin , irinotecan , and oxaliplatin ( FOLFIRINOX ) leads to longer overall survival than gemcitabine therapy . We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer . METHODS We r and omly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen ( oxaliplatin [ 85 mg per square meter of body‐surface area ] , irinotecan [ 180 mg per square meter , reduced to 150 mg per square meter after a protocol ‐specified safety analysis ] , leucovorin [ 400 mg per square meter ] , and fluorouracil [ 2400 mg per square meter ] every 2 weeks ) or gemcitabine ( 1000 mg per square meter on days 1 , 8 , and 15 every 4 weeks ) for 24 weeks . The primary end point was disease‐free survival . Secondary end points included overall survival and safety . RESULTS At a median follow‐up of 33.6 months , the median disease‐free survival was 21.6 months in the modified‐FOLFIRINOX group and 12.8 months in the gemcitabine group ( stratified hazard ratio for cancer‐related event , second cancer , or death , 0.58 ; 95 % confidence interval [ CI ] , 0.46 to 0.73 ; P<0.001 ) . The disease‐free survival rate at 3 years was 39.7 % in the modified‐FOLFIRINOX group and 21.4 % in the gemcitabine group . The median overall survival was 54.4 months in the modified‐FOLFIRINOX group and 35.0 months in the gemcitabine group ( stratified hazard ratio for death , 0.64 ; 95 % CI , 0.48 to 0.86 ; P=0.003 ) . The overall survival rate at 3 years was 63.4 % in the modified‐FOLFIRINOX group and 48.6 % in the gemcitabine group . Adverse events of grade 3 or 4 occurred in 75.9 % of the patients in the modified‐FOLFIRINOX group and in 52.9 % of those in the gemcitabine group . One patient in the gemcitabine group died from toxic effects ( interstitial pneumonitis ) . CONCLUSIONS Adjuvant therapy with a modified FOLFIRINOX regimen led to significantly longer survival than gemcitabine among patients with resected pancreatic cancer , at the expense of a higher incidence of toxic effects . ( Funded by R&D Unicancer and others ; Clinical Trials.gov number , NCT01526135 ; EudraCT number , 2011‐002026‐52 .
The effectiveness of neoadjuvant therapy ( NAT ) remains unclear in resectable pancreatic cancer ( PC ) as compared with upfront surgery ( US ) .
The aim of this study was to investigate the survival gain of NAT over US in resectable PC .