***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: ABSTRACT Aim : Gemcitabine ( GEM ) and nab-paclitaxel ( nab-P ) significantly improved overall survival over GEM in metastatic pancreatic adenocarcinoma ( PA ) . Given the synergism of taxanes with platinum compounds and fluoropyrimidines , we determined the recommended phase 2 dose ( RP2D ) of nab-P in combination with cisplatin , capecitabine , and GEM ( PAXG regimen ) in a phase Ib trial in patients ( pts ) with stage III PA ( NCT01730222 ) . Methods : GEM , cisplatin and capecitabine were given at fixed dose ( 800 , 30 , and 1250 mg/m2 , respectively ) q 2 weeks . Doses of nab-P were escalated in cohorts of 3 to 6 pts from 100 ( level 1 ) , to 125 ( level 2 ) and 150 mg/m2 ( level 3 ) q 2 weeks . The maximum tolerated dose ( MTD ) was defined as the dose at which > 2 out of 3 - 6 pts developed dose-limiting toxicity ( DLT ) during the first month of therapy . DLT was defined as G ≥ 4 neutropenia lasting ≥ 7 days ; G ≥ 3 febrile neutropenia , fever ≥38.5 ° C , thrombocytopenia , diarrhea , nausea or vomiting ; G ≥ 2 neurological toxicity or failure to recover to grade ≤ 1 toxicity ( except alopecia ) or to baseline values after delaying the initiation of next cycle by > 2 weeks . Results : Between Dec 2012 and Mar 2014 , 23 pts ( 16 males ; median age 63 years ) with unresectable ( according to a surgical team performing > 100 duodenocephalopancreasectomy/year ) stage III PA , were enrolled at a single institution ( 3 at level 1 , 5 at level 2 , 15 at level 3 ) . To date , 197 cycles of PAXG were administered . Therapy is ongoing in 5 pts at level 3 . No DLT has occurred . Worse per patient toxicity was G3/4 neutropenia 29/29 % ; G3 fatigue 14 % ; G3 neuropathy , anemia , nausea , diarrhea 7 % . After 123 cycles at 150 mg/m2 the nab-P dose-intensity was 90 % . To date , a partial response ( PR ) was observed in 15 pts ( 65 % ) and stable disease ( SD ) in 8 pts ; among 20 pts with positive PET scan a complete response was observed in 8 ( 40 % ) , PR in 10 ( 50 % ) , SD in 2 ; 19 pts had elevated basal CA19 - 9 which was reduced by > 50 % in 18 ( 95 % ) ; 15/16 ( 94 % ) pts with mature follow-up were progression-free at 6 months from therapy start . Conclusions : The RP2D of nab-P in the PAXG regimen was 150 mg/m2 every 2 weeks . Preliminary results are promising and a phase II r and omized trial with this regimen is ongoing . Disclosure : M. Reni : Participation in an Advisory Board : Merck ; Celgene ; CLOVIS ; Genentech ; Boehringer L. Gianni : advisory board Celgene . All other authors have declared no conflicts of interest Purpose Addition of either nab-paclitaxel or erlotinib to gemcitabine to treat advanced pancreatic cancer has demonstrated overall survival benefit . This study was conducted to evaluate the tolerability and safety of combining all three drugs and assess preliminary evidence of efficacy . Methods In this open-label , phase 1b study , patients with previously untreated , advanced pancreatic cancer were treated in 28-day cycles with intravenous gemcitabine/nab-paclitaxel on days 1 , 8 , and 15 , and once daily oral erlotinib . A st and ard “ 3 + 3 ” design was used . Dose level 1 ( DL1 ) for gemcitabine (mg/m2)/nab-paclitaxel (mg/m2)/erlotinib ( mg ) was 1000/125/100 , respectively , with de-escalation to DL−1 ( 1000/100/100 ) , DL−2b ( 1000/75/100 ) , and DL−3 ( 1000/75/75 ) . The maximum tolerated dose ( MTD ) was defined by occurrence of dose-limiting toxicity ( DLT ) in ≤1 of six patients within the first cycle . Efficacy was assessed with CT scans performed at two-cycle intervals . Results Nineteen patients were enrolled . DLTs occurred in two patients at DL1 , three patients at DL−1 , two patients at DL−2b , and one patient at DL−3 . The MTD for the combination of gemcitabine/nab-paclitaxel/erlotinib was DL−3 ( 1000/75/75 ) . In analyses of efficacy among 14 evaluable patients , partial responses were observed in four of six patients at DL1 , one of two patients at DL−2b , and two of six patients at DL−3 . Conclusion The addition of erlotinib to gemcitabine and nab-paclitaxel is not tolerable at st and ard single-agent dosing of all drugs . However , significant clinical activity was noted , even at DL−3 . Further study of the combination will need to incorporate reduced dosing PURPOSE To provide evidence -based recommendations to oncologists and others for treatment of patients with locally advanced , unresectable pancreatic cancer . METHODS American Society of Clinical Oncology convened an Expert Panel of medical oncology , radiation oncology , surgical oncology , gastroenterology , palliative care , and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015 . Outcomes included overall survival , disease-free survival , progression-free survival , and adverse events . RESULTS Twenty-six r and omized controlled trials met the systematic review criteria . RECOMMENDATIONS A multiphase computed tomography scan of the chest , abdomen , and pelvis should be performed . Baseline performance status and comorbidity profile should be evaluated . The goals of care , patient preferences , psychological status , support systems , and symptoms should guide decisions for treatments . A palliative care referral should occur at first visit . Initial systemic chemotherapy ( 6 months ) with a combination regimen is recommended for most patients ( for some patients radiation therapy may be offered up front ) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile . There is no clear evidence to support one regimen over another . The gemcitabine-based combinations and treatments recommended in the metastatic setting ( eg , fluorouracil , leucovorin , irinotecan , and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel ) have not been evaluated in r and omized controlled trials involving locally advanced , unresectable pancreatic cancer . If there is local disease progression after induction chemotherapy , without metastasis , then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile . If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities , radiation therapy may be offered as an alternative . Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline . Follow-up visits every 3 to 4 months are recommended . Additional information is available at www.asco.org/ guidelines /LAPC and www.asco.org/ guidelines /MetPC and www.asco.org/ guidelines wiki PURPOSE The trial objectives were to identify the maximum-tolerated dose ( MTD ) of first-line gemcitabine plus nab-paclitaxel in metastatic pancreatic adenocarcinoma and to provide efficacy and safety data . Additional objectives were to evaluate positron emission tomography ( PET ) scan response , secreted protein acidic and rich in cysteine ( SPARC ) , and CA19 - 9 levels in relation to efficacy . Subsequent pre clinical studies investigated the changes involving the pancreatic stroma and drug uptake . PATIENTS AND METHODS Patients with previously untreated advanced pancreatic cancer were treated with 100 , 125 , or 150 mg/m(2 ) nab-paclitaxel followed by gemcitabine 1,000 mg/m(2 ) on days 1 , 8 , and 15 every 28 days . In the pre clinical study , mice were implanted with human pancreatic cancers and treated with study agents . RESULTS A total of 20 , 44 , and three patients received nab-paclitaxel at 100 , 125 , and 150 mg/m(2 ) , respectively . The MTD was 1,000 mg/m(2 ) of gemcitabine plus 125 mg/m(2 ) of nab-paclitaxel once a week for 3 weeks , every 28 days . Dose-limiting toxicities were sepsis and neutropenia . At the MTD , the response rate was 48 % , with 12.2 median months of overall survival ( OS ) and 48 % 1-year survival . Improved OS was observed in patients who had a complete metabolic response on [(18)F]fluorodeoxyglucose PET . Decreases in CA19 - 9 levels were correlated with increased response rate , progression-free survival , and OS . SPARC in the stroma , but not in the tumor , was correlated with improved survival . In mice with human pancreatic cancer xenografts , nab-paclitaxel alone and in combination with gemcitabine depleted the desmoplastic stroma . The intratumoral concentration of gemcitabine  was increased by 2.8-fold in mice receiving nab-paclitaxel plus gemcitabine versus those receiving gemcitabine alone . CONCLUSION The regimen of nab-paclitaxel plus gemcitabine has tolerable adverse effects with substantial antitumor activity , warranting phase III evaluation 
    Output:
    
Ongoing trials are investigating nab-P/Gem with or without other agents across disease setting s. Discussion Studies conducted after MPACT have demonstrated that nab-P/Gem is an effective regimen for the first-line treatment of MPC for a wide range of patients .
Ongoing studies will yield valuable insights on the utility of nab-P – containing regimens to improve patient outcomes in PC in both earlier-stage and advanced disease