***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background First-line treatment with FOLFIRINOX significantly increases overall survival ( OS ) in patients with metastatic pancreatic adenocarcinoma ( PA ) compared with gemcitabine . The aim of this observational cohort was to evaluate the tolerability and efficacy of this regimen in unresectable locally advanced PA ( LAPA ) . Patients and Methods From February 2010 to February 2012 , all consecutive patients from 11 French centers treated by FOLFIRINOX for a histologically proven LAPA were prospect ively enrolled . Unresectability was defined independently by each center ’s multidisciplinary staff at diagnosis . Absence of metastatic disease was confirmed by chest-abdomen-pelvis computed tomography scan . FOLFIRINOX was delivered every 2 weeks as previously reported until progressive disease , major toxicity , or consolidation treatment by radiotherapy and /or surgery . Results Seventy-seven patients were enrolled . They received a median number of five cycles ( 1–30 ) . Grade 3–4 toxicities were neutropenia ( 11 % ) , nausea ( 9 % ) , diarrhea ( 6 % ) , fatigue ( 6 % ) , and anemia ( 1 % ) . Grade 2–3 sensory neuropathy occurred in 25 % of patients . No toxic death was reported and only 6 % of patients had to stop treatment because of toxicity . Disease control rate was 84 with 28 % of objective response ( Response Evaluation Criteria in Solid Tumors ) . Seventy-five percent of patients received a consolidation therapy : 70 % had radiotherapy and 36 % underwent a surgical resection , with a curative intent . Within the whole cohort , 1-year OS rate was 77 % ( 95 % CI 65–86 ) and 1-year progression-free survival rate was 59 % ( 95 % CI 46–70 ) . Conclusion First-line FOLFIRINOX for LAPA seems to be effective and have a manageable toxicity profile . These promising results will have to be confirmed in a phase III r and omized trial Background FOLFIRINOX ( FX ) has been reported as an effective treatment for unresectable advanced pancreatic cancer . However , FX is associated with a high incidence of adverse events ( AEs ) . A previous phase II study in Japan showed high incidences of hematological AEs , including febrile neutropenia ( 22.2 % ) . A modified FX regimen ( mFX ) may decrease the rates of AEs and be more effective than FX by improving the treatment compliance . Aims To assess the safety and efficacy of first-line mFX for unresectable advanced pancreatic cancer . Patients and methods This was as a multicenter prospect i ve phase II study in chemotherapy-naïve Japanese patients with pathologically confirmed unresectable advanced pancreatic adenocarcinoma or adenosquamous carcinoma . Treatment with mFX ( 85 mg/m2 oxaliplatin , 150 mg/m2 irinotecan , and 200 mg/m2 l-leucovorin , followed by 46-h continuous infusion of 2400 mg/m2 5-fluorouracil ) was administered every 2 weeks . The primary endpoint was the response rate . The secondary endpoints were overall survival , progression-free survival , and safety .  Results Thirty-one patients ( 18 men ; median age , 64 years ) were enrolled . A median of 13 treatment cycles were administered during a median follow-up period of 14.2 months . The response rate , median overall survival , and median progression-free survival were 38.7 % , 14.9 months , and 7.0 months , respectively . Grade 3 or 4 AEs included neutropenia ( 83.9 % ) , febrile neutropenia ( 16.1 % ) , peripheral sensory neuropathy ( 9.7 % ) , thrombocytopenia ( 6.5 % ) , diarrhea ( 6.5 % ) , anorexia ( 6.5 % ) , and vomiting ( 3.2 % ) . Conclusion Compared to FX , mFX may result in fewer Grade 3 or 4 non-hematological AEs , with a comparable response rate . However , further efforts might be required to reduce hematological AEs Objectives : The combination of 5-fluorouracil ( 5-FU ) , irinotecan and oxaliplatin ( FOLFIRINOX ) is considered the first-line chemotherapy for fit patients with advanced pancreatic ductal adenocarcinoma ( PDAC ) but carries an unfavourable adverse event ( AE ) profile . We retrospectively evaluated the tolerability and efficacy of a modified FOLFIRINOX ( mFOLFIRINOX ) regimen : intravenous oxaliplatin 85 mg/m2 , irinotecan 135 mg/m2 , folinic acid 400 mg/m2 and 5-FU infusion 2,400 mg/m2 over 46 h , with routine subcutaneous filgrastim on a 14-day cycle . Methods : Records of 18 patients with advanced PDAC who received treatment with mFOLFIRINOX  were review ed . Imaging of measurable disease was assessed for response , and survival was measured from the date of commencing chemotherapy to disease progression and /or death . Results : Grade 3 or 4 AEs ( n ; % ) included vomiting ( 5 ; 28 ) , nausea ( 4 ; 22 ) , diarrhoea ( 3 ; 17 ) and non-neutropaenic fever ( 3 ; 17 ) . For patients with stage IV disease , 12/15 ( 80 % ) achieved at least stable disease as the best radiological response , with 7/15 ( 47 % ) objective responses . In this subgroup , median overall and progression-free survival were 9.3 months ( 95 % CI 8.3 - 10.4 ) and 7.2 months ( 95 % CI 4.7 - 9.6 ) , respectively . Conclusion : Compared to full-dose FOLFIRINOX , our modified regimen result ed in lower haematological but only marginally improved non-haematological toxicity rates , with comparable efficacy outcomes . Prospect i ve studies are required to vali date these findings BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine  ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine  ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group , as compared with 3.7 months in the gemcitabine group ( hazard ratio for disease progression or death , 0.69 ; 95 % CI , 0.58 to 0.82 ; P<0.001 ) ; the response rate according to independent review was 23 % versus 7 % in the two groups ( P<0.001 ) . The most common adverse events of grade 3 or higher were neutropenia ( 38 % in the nab-paclitaxel-gemcitabine group vs. 27 % in the gemcitabine group ) , fatigue ( 17 % vs. 7 % ) , and neuropathy ( 17 % vs. 1 % ) . Febrile neutropenia occurred in 3 % versus 1 % of the patients in the two groups . In the nab-paclitaxel-gemcitabine group , neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days . CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma , nab-paclitaxel plus gemcitabine significantly improved overall survival , progression-free survival , and response rate , but rates of peripheral neuropathy and myelosuppression were increased . ( Funded by Celgene ; Clinical Trials.gov number , NCT00844649 . ) CONTEXT Combination chemotherapy with FOLFIRINOX ( oxaliplatin , irinotecan , fluorouracil , and leucovorin ) was shown to be effective in a large phase III trial . OBJECTIVE The purpose of this study was to examine the tolerance and effectiveness of FOLFIRINOX as practice d outside of the confines of a clinical trial and to document any dose modifications used by practicing oncologists . METHODS Data on patients with all stages of pancreatic adenocarcinoma treated with FOLFIRINOX at three institutions was analyzed for efficacy , tolerance , and use of any dose modifications . RESULTS Total of 61 patients was included in this review . Median age was 58 years ( range : 37 to 72 years ) , 33 were male ( 54.1 % ) and majority had ECOG performance of 0 or 1 ( 86.9 % , 53 patients ) . Thirty-eight ( 62.3 % ) had metastatic disease , while 23 ( 37.7 % ) were treated for locally advanced or borderline resectable disease . Patients were treated with a median number of four cycles of FOLFIRINOX , with dose modifications in 58.3 % ( 176/302 ) of all cycles . Ten patients had stable disease ( 16.4 % ) , four had a partial response ( 6.6 % ) while eight had progressive disease ( 13.1 % ) on best imaging following therapy . Median progression-free survival and overall survival were 7.5 months and 13.5 months , respectively . The most common grade 3 - 4 adverse event was neutropenia at 19.7 % ( 12 cases ) , with 4.9 % ( 3 cases ) rate of febrile neutropenia . Twenty-one patients ( 34.4 % ) were hospitalized as a result of therapy but there were no therapy-related deaths . Twenty-three ( 37.7 % ) had therapy eventually discontinued as a result of adverse events . CONCLUSION Despite substantial rates of adverse events and use of dose modifications , FOLFIRINOX was found to be clinical ly effective in both metastatic and non-metastatic patients .  Regimen toxicity did not detract from overall response and survival PURPOSE To evaluate response rate and toxicity of irinotecan and oxaliplatin plus fluorouracil ( FU ) and leucovorin ( Folfirinox ) in advanced pancreatic adenocarcinoma ( APA ) . PATIENTS AND METHODS Chemotherapy-naive patients with histologically proven APA and bidimensionally measurable disease were treated with Folfirinox therapy every 2 weeks , which comprised oxaliplatin 85 mg/m(2 ) and irinotecan 180 mg/m(2 ) plus leucovorin 400 mg/m(2 ) followed by bolus FU 400 mg/m(2 ) on day 1 , then FU 2,400 mg/m(2 ) as a 46-hour continuous infusion . Quality of life ( QOL ) was assessed using European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 ( EORTC QLQ-C30 ) . RESULTS Forty-seven patients were entered , and 46 received treatment . Thirty-five patients ( 76 % ) had metastatic disease . A total of 356 cycles were delivered , with a median of eight cycles per patient ( range , one to 24 cycles ) . All patients were assessable for safety . No toxic death occurred . Grade 3 to 4 neutropenia occurred in 52 % of patients , including two patients with febrile neutropenia . Other relevant toxicities included grade 3 to 4 nausea ( 20 % ) , vomiting ( 17 % ) , and diarrhea ( 17 % ) and grade 3 neuropathy ( 15 % ; Levi 's scale ) . The confirmed response rate was 26 % ( 95 % CI , 13 % to 39 % ) , including 4 % complete 
    Output:
    
In conclusion , modified FOLFIRINOX could provide comparative survival benefits with fewer adverse events compared to the conventional dosage