2024
Palliative Care and End-of-Life Care in Metastatic Pancreatic Cancer
O’Brien J, Halsey B, Connors M, Deng M, Handorf E, Berardi G, Lynch S, Sorice K, Reddy S, Meyer J, Bauman J, Dotan E. Palliative Care and End-of-Life Care in Metastatic Pancreatic Cancer. Journal Of Palliative Medicine 2024, 28: 217-223. PMID: 39636708, DOI: 10.1089/jpm.2024.0313.Peer-Reviewed Original ResearchEnd of lifeAggressive EOL carePalliative careDay of deathEOL carePC consultationIntegration of palliative careEnd of life careEnd-of-life careAssociated with worse qualityHealth care resourcesMetastatic pancreatic cancerQuality of lifePC teamAggressive careCare resourcesHospiceAverage length of timeTertiary cancer centerCareWorse qualityAverage timeCancer CenterBenefit patientsPancreatic cancer
2023
Nimotuzumab Plus Gemcitabine for K-Ras Wild-Type Locally Advanced or Metastatic Pancreatic Cancer
Qin S, Li J, Bai Y, Wang Z, Chen Z, Xu R, Xu J, Zhang H, Chen J, Yuan Y, Liu T, Yang L, Zhong H, Chen D, Shen L, Hao C, Fu D, Cheng Y, Yang J, Wang Q, Qin B, Pan H, Zhang J, Bai X, Zheng Q. Nimotuzumab Plus Gemcitabine for K-Ras Wild-Type Locally Advanced or Metastatic Pancreatic Cancer. Journal Of Clinical Oncology 2023, 41: 5163-5173. PMID: 37647576, PMCID: PMC10666986, DOI: 10.1200/jco.22.02630.Peer-Reviewed Original ResearchConceptsProgression-free survivalK-ras wild-type tumorMetastatic pancreatic cancerWild-type tumorsOverall survivalPancreatic cancerK-rasMedian progression-free survivalProgression-free survival timePhase III clinical studiesK-ras wild-typeResponse rateIncidence of adverse eventsDisease control rateSecondary end pointsIII clinical studiesPhase IIb trialMean survival timeMedian OSNimotuzumab groupImproved OSPlacebo groupClinical benefitSafety profileAdverse events
2022
Phase 3, multicenter, randomized study of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) as first-line therapy for patients with metastatic adenocarcinoma of the pancreas (AVENGER500).
Philip P, Bahary N, Mahipal A, Kasi A, Lima C, Alistar A, Oberstein P, Golan T, Sahai V, Metges J, Lacy J, Fountzilas C, Lopez C, Ducreux M, Hammel P, Salem M, Bajor D, Benson A, Buyse M, Van Cutsem E. Phase 3, multicenter, randomized study of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) as first-line therapy for patients with metastatic adenocarcinoma of the pancreas (AVENGER500). Journal Of Clinical Oncology 2022, 40: 4023-4023. DOI: 10.1200/jco.2022.40.16_suppl.4023.Peer-Reviewed Original ResearchProgression-free survivalMetastatic pancreatic cancerOverall response rateMedian overall survivalFirst-line therapyCPI-613Experimental armRandomized phase 3 trialStandard first-line therapyTreatment-emergent adverse eventsDoses of irinotecanTreatment-naïve patientsPhase 3 trialDuration of responseLimited treatment optionsPatient reported outcomesTest armIntolerable toxicityPrimary endpointSecondary endpointsAdverse eventsOverall survivalMetastatic adenocarcinomaTreatment optionsControl armKRYSTAL-1: Updated activity and safety of adagrasib (MRTX849) in patients (Pts) with unresectable or metastatic pancreatic cancer (PDAC) and other gastrointestinal (GI) tumors harboring a KRASG12C mutation.
Bekaii-Saab T, Spira A, Yaeger R, Buchschacher G, McRee A, Sabari J, Johnson M, Barve M, Hafez N, Velastegui K, Christensen J, Kheoh T, Der-Torossian H, Rybkin I. KRYSTAL-1: Updated activity and safety of adagrasib (MRTX849) in patients (Pts) with unresectable or metastatic pancreatic cancer (PDAC) and other gastrointestinal (GI) tumors harboring a KRASG12C mutation. Journal Of Clinical Oncology 2022, 40: 519-519. DOI: 10.1200/jco.2022.40.4_suppl.519.Peer-Reviewed Original ResearchDisease control rateKRAS G12C mutationProgression-free survivalPartial responseGI tumorsClinical activityG12C mutationPancreatic cancerSolid tumorsMedian progression-free survivalTreatment-related adverse eventsGrade 3/4 eventsGrade 5 eventsPhase 1/2 studyAdvanced solid tumorsMetastatic pancreatic cancerMetastatic solid tumorsEncouraging clinical activityPhase 2 cohortExtensive tissue distributionKRAS G12C inhibitorsFavorable pharmacokinetic propertiesEvaluable ptsKRASG12C mutationData cutoff
2021
Clinical outcomes of first line FOLFIRINOX vs . gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System
Patel T, Miccio J, Cecchini M, Srikumar T, Stein S, Kortmanksy J, Johung K, Lacy J. Clinical outcomes of first line FOLFIRINOX vs . gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System. Journal Of Gastrointestinal Oncology 2021, 0: 0-0. PMID: 35070386, PMCID: PMC8748034, DOI: 10.21037/jgo-21-202.Peer-Reviewed Original ResearchMetastatic pancreatic cancerFirst-line FOLFIRINOXTreatment discontinuationFFX groupDose modificationOverall survivalNab-paclitaxelPancreatic cancerGN groupComparative effectivenessMedian TTDFirst-line settingMedian overall survivalOutcomes of patientsTreatment-related toxicityFirst-line therapyKaplan-Meier methodRate of hospitalizationElectronic medical record systemAdjuvant gemcitabineChemotherapy toxicityDiscontinuation ratesLine therapyMedical record systemTreatment toxicityAn Interdisciplinary Approach to Metastatic Pancreatic Cancer and Comorbid Opioid Use Disorder Treatment Within a VA Health Care System.
Ruskin A, Falker CG, Edens EL, Bauer MR. An Interdisciplinary Approach to Metastatic Pancreatic Cancer and Comorbid Opioid Use Disorder Treatment Within a VA Health Care System. Federal Practitioner 2021, 38: s66-s71. PMID: 34733097, PMCID: PMC8560123, DOI: 10.12788/fp.0160.Peer-Reviewed Original ResearchPancreatic cancerOpioid use disorder treatmentVA health care systemActive substance use disorderAdvanced pancreatic cancerMetastatic pancreatic cancerUse disorder treatmentSubstance use disordersHealth care systemUse disordersDisorder treatmentCancer treatmentCare systemMultidisciplinary approachCancerTreatmentPatients
2020
A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma
Hayashi A, Fan J, Chen R, Ho Y, Makohon-Moore A, Lecomte N, Zhong Y, Hong J, Huang J, Sakamoto H, Attiyeh M, Kohutek Z, Zhang L, Boumiza A, Kappagantula R, Baez P, Bai J, Lisi M, Chadalavada K, Melchor J, Wong W, Nanjangud G, Basturk O, O’Reilly E, Klimstra D, Hruban R, Wood L, Overholtzer M, Iacobuzio-Donahue C. A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma. Nature Cancer 2020, 1: 59-74. PMID: 35118421, PMCID: PMC8809486, DOI: 10.1038/s43018-019-0010-1.Peer-Reviewed Original ResearchConceptsExpression profilesSquamous featuresPancreatic cancerChromatin modifier genesCancer expression profilesMetastatic pancreatic cancerEvolution of pancreatic cancerBasal-like phenotypeBasal-like subtypePhylogenetic studiesChromatin modifiersEvolutionary analysisPancreatic ductal adenocarcinomaTranscriptional heterogeneityModifier genesIntercellular heterogeneitySubclonal populationsSquamous histologyMYC amplificationGlandular tumorsSomatic mutationsSquamous morphologyClonal mutationsDuctal adenocarcinomaHistologic correlation
2019
Serum gamma-glutamyltransferase and the overall survival of metastatic pancreatic cancer
Xiao Y, Yang H, Lu J, Li D, Xu C, Risch HA. Serum gamma-glutamyltransferase and the overall survival of metastatic pancreatic cancer. BMC Cancer 2019, 19: 1020. PMID: 31664937, PMCID: PMC6819453, DOI: 10.1186/s12885-019-6250-8.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaMetastatic pancreatic ductal adenocarcinomaOverall survivalSerum GGTSignificant dose-response associationCox proportional hazards modelMetastatic PDAC patientsDose-response associationMetastatic pancreatic cancerPancreatic cancer survivalSpecialized cancer hospitalBlood glucose levelsProportional hazards modelHazard ratioPrognostic roleCancer HospitalPDAC patientsCancer survivalSubgroup analysisPancreatic cancerDuctal adenocarcinomaMetastatic PCCancer occurrenceGlucose levelsMortality riskPhase IB/II Randomized Study of FOLFIRINOX Plus Pegylated Recombinant Human Hyaluronidase Versus FOLFIRINOX Alone in Patients With Metastatic Pancreatic Adenocarcinoma: SWOG S1313
Ramanathan RK, McDonough SL, Philip PA, Hingorani SR, Lacy J, Kortmansky JS, Thumar J, Chiorean EG, Shields AF, Behl D, Mehan PT, Gaur R, Seery T, Guthrie KA, Hochster HS. Phase IB/II Randomized Study of FOLFIRINOX Plus Pegylated Recombinant Human Hyaluronidase Versus FOLFIRINOX Alone in Patients With Metastatic Pancreatic Adenocarcinoma: SWOG S1313. Journal Of Clinical Oncology 2019, 37: jco.18.01295. PMID: 30817250, PMCID: PMC6494359, DOI: 10.1200/jco.18.01295.Peer-Reviewed Original ResearchConceptsMetastatic pancreatic cancerMedian overall survivalCombination armOverall survivalHazard ratioControl armPhase II open-label studyTreatment-related grade 3Adequate organ functionPhase II dosageOpen-label studyPrimary end pointMetastatic pancreatic adenocarcinomaOS hazard ratioHA statusDose-finding studyInterim futility analysisRecombinant human hyaluronidaseEnoxaparin prophylaxisThromboembolic eventsPerformance statusProlong survivalRandomized studyFutility analysisGood PS
2018
Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors
Andricovich J, Perkail S, Kai Y, Casasanta N, Peng W, Tzatsos A. Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors. Cancer Cell 2018, 33: 512-526.e8. PMID: 29533787, PMCID: PMC5854186, DOI: 10.1016/j.ccell.2018.02.003.Peer-Reviewed Original ResearchConceptsPancreatic cancerCOMPASS-like complexesBET inhibitorsMetastatic pancreatic cancerSensitivity to BET inhibitorsSubtypes of tumorsSpectrum of malignanciesPatient-tailored therapySuper-enhancersActivation of super-enhancersSquamous-likeTumor suppressor functionSquamous differentiationRestrained tumor growthTailored therapyTumor growthTherapeutic nicheKDM6A lossSuppressor functionAberrant activationKDM6ACancerCharacterized mechanismsInhibitorsConcomitant loss
2017
EGFR Exon 19 Deletion in Pancreatic Adenocarcinoma Responds to Erlotinib, Followed by T790M-Mediated Resistance.
Cecchini M, Sklar J, Lacy J. EGFR Exon 19 Deletion in Pancreatic Adenocarcinoma Responds to Erlotinib, Followed by T790M-Mediated Resistance. Journal Of The National Comprehensive Cancer Network 2017, 15: 1085-1089. PMID: 28874593, DOI: 10.6004/jnccn.2017.0151.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaTyrosine kinase inhibitorsMetastatic pancreatic ductal adenocarcinomaEGFR Exon 19 DeletionEGFR tyrosine kinase inhibitorsImmune checkpoint inhibitorsMetastatic pancreatic cancerExon 19 deletionsEpidermal growth factor receptorGrowth factor receptorAdvanced diseaseCheckpoint inhibitorsMultidrug chemotherapyPancreatic cancerDisease progressionDuctal adenocarcinomaPancreatic adenocarcinomaActionable mutationsTumor typesKinase inhibitorsExon 19Factor receptorAdenocarcinomaPatientsErlotinib
2016
Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer
Stein SM, James ES, Deng Y, Cong X, Kortmansky JS, Li J, Staugaard C, Indukala D, Boustani AM, Patel V, Cha CH, Salem RR, Chang B, Hochster HS, Lacy J. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. British Journal Of Cancer 2016, 114: 737-743. PMID: 27022826, PMCID: PMC4984865, DOI: 10.1038/bjc.2016.45.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCamptothecinFemaleFluorouracilFollow-Up StudiesHumansIrinotecanLeucovorinLiver NeoplasmsLung NeoplasmsLymphatic MetastasisMaleMiddle AgedNeoplasm StagingOrganoplatinum CompoundsOxaliplatinPancreatic NeoplasmsPeritoneal NeoplasmsPrognosisProspective StudiesSurvival RateConceptsProgression-free survivalAdvanced pancreatic cancerPhase II studyOverall survivalAdverse eventsPancreatic cancerII studyResponse rateMedian progression-free survivalMulticentre phase II studyFluorodeoxyglucose positron emission tomographyUse of FOLFIRINOXMedian overall survivalHistorical control patientsMetastatic pancreatic cancerFirst prospective studyPositron emission tomographyControl patientsMetastatic diseaseProspective studyProspective dataFOLFIRINOXLAPCEmission tomographyPatientsRandomized Phase II Trial of Irinotecan/Docetaxel or Irinotecan/Docetaxel Plus Cetuximab for Metastatic Pancreatic Cancer
Burtness B, Powell M, Catalano P, Berlin J, Liles DK, Chapman AE, Mitchell E, Benson AB. Randomized Phase II Trial of Irinotecan/Docetaxel or Irinotecan/Docetaxel Plus Cetuximab for Metastatic Pancreatic Cancer. American Journal Of Clinical Oncology 2016, 39: 340-345. PMID: 24685886, PMCID: PMC4177955, DOI: 10.1097/coc.0000000000000068.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAnticoagulantsAntineoplastic Combined Chemotherapy ProtocolsCA-19-9 AntigenCamptothecinCetuximabDiarrheaDisease-Free SurvivalDocetaxelEnoxaparinFemaleHumansIrinotecanMaleMiddle AgedPancreatic NeoplasmsResponse Evaluation Criteria in Solid TumorsSurvival RateTaxoidsThromboembolismConceptsProgression-free survivalMetastatic pancreatic cancerAddition of cetuximabGrade 3/4 toxicitiesOverall survivalArm APancreatic cancerResponse rateArm B.Arm B. Median progression-free survivalMedian progression-free survivalPrincipal grade 3/4 toxicitiesRandomized phase II trialIrinotecan/docetaxelPhase II trialEligible patientsII trialPrimary endpointSecondary endpointsThromboembolic eventsDocetaxel combinationIrinotecan combinationObjective responseIrinotecan therapyMetastatic adenocarcinomaFinal analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer.
Stein S, James E, Cong X, Deng Y, Salem R, Cha C, Chang B, Hochster H, Doddamane I, Boustani A, Patel V, Kortmansky J, Li J, Staugaard C, Lacy J. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Journal Of Clinical Oncology 2016, 34: 395-395. DOI: 10.1200/jco.2016.34.4_suppl.395.Peer-Reviewed Original Research
2015
Final analysis of a phase II study of Yale-modified FOLFIRINOX (mFOLFIRINOX) in metastatic pancreatic cancer (MPC).
James E, Cong X, Yao X, Hahn C, Kaley K, Li J, Kortmansky J, Fischbach N, Cha C, Salem R, Stein S, Hochster H, Lacy J. Final analysis of a phase II study of Yale-modified FOLFIRINOX (mFOLFIRINOX) in metastatic pancreatic cancer (MPC). Journal Of Clinical Oncology 2015, 33: 395-395. DOI: 10.1200/jco.2015.33.3_suppl.395.Peer-Reviewed Original ResearchMetastatic pancreatic cancerResponse rateProphylactic pegfilgrastimEntire cohortPhase II open-label studyFinal analysisECOG PS 0ECOG PS 0/1Grade 3/4 toxicitiesOpen-label studyPhase II studyBolus 5FUPS 0/1Febrile neutropeniaLAPC patientsPeritoneal diseaseII studyPS 0Surgical resectionUnacceptable toxicityImproved tolerabilityPeripheral neuropathyMetastatic sitesPancreatic cancerFOLFIRINOX
2014
Interim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC).
James E, Yao X, Cong X, Li J, Hahn C, Kaley K, Kortmansky J, Fischbach N, Chang B, Salem R, Cha C, Stein S, Hochster H, Lacy J. Interim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC). Journal Of Clinical Oncology 2014, 32: e15226-e15226. DOI: 10.1200/jco.2014.32.15_suppl.e15226.Peer-Reviewed Original ResearchSrc inhibition through a phase II study of 5-fluorouracil, oxaliplatin, plus dasatinib (FOLFOX-D) in first-line metastatic pancreatic adenocarcinoma.
George T, Ivey A, Daily K, Dang L, Watson S, Granicz R, Tormes K, Lu X, Liu C, Allegra C, Behrns K, Hughes S, Ogunwobi O, Trevino J. Src inhibition through a phase II study of 5-fluorouracil, oxaliplatin, plus dasatinib (FOLFOX-D) in first-line metastatic pancreatic adenocarcinoma. Journal Of Clinical Oncology 2014, 32: 319-319. DOI: 10.1200/jco.2014.32.3_suppl.319.Peer-Reviewed Original ResearchMetastatic pancreatic cancerProgression-free survivalGrade 3 AEsOverall survivalOral multi-tyrosine kinase inhibitorMedian progression-free survivalMulti-tyrosine kinase inhibitorSrc inhibitionAdequate organ functionBiochemical response rateECOG PS 0Grade 4 AEsGrade 5 toxicityRECIST measurable diseaseTriplet combination therapyPhase II studyMetastatic pancreatic adenocarcinomaClinical unmet needPredictors of responseQuality of lifeEligible ptsMFOLFOX6 chemotherapyMeasurable diseasePrior therapySecondary endpointsInterim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC).
James E, Yao X, Cong X, Stein S, Kaley K, Hahn C, Cha C, Salem R, Hochster H, Lacy J. Interim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC). Journal Of Clinical Oncology 2014, 32: 256-256. DOI: 10.1200/jco.2014.32.3_suppl.256.Peer-Reviewed Original ResearchMetastatic pancreatic cancerAdvanced pancreatic cancerPancreatic cancerFebrile neutropeniaResponse rateEvaluable ptsProphylactic pegfilgrastimInterim analysisPhase II open-label studyGrade 3/4 toxicitiesOpen-label studyPhase II studyFDG-PET scansSimilar response ratesECOG PSNeoadjuvant FOLFIRINOXUnderwent resectionII studySurgical resectionUnacceptable toxicityPET responseFOLFIRINOXRetrospective analysisDose reductionLabel study
2013
Emerging concepts in combination chemotherapy for metastatic pancreatic cancer: A systematic review of randomized controlled trials.
Njei B, Ditah I, Shimanovsky A, Owusu P, Birk J. Emerging concepts in combination chemotherapy for metastatic pancreatic cancer: A systematic review of randomized controlled trials. Journal Of Clinical Oncology 2013, 31: 228-228. DOI: 10.1200/jco.2013.31.4_suppl.228.Peer-Reviewed Original ResearchProgression-free survivalMetastatic pancreatic cancerPlatinum-containing regimensOverall survivalPancreatic cancerAdverse eventsRandomized Controlled TrialsCombination chemotherapyProlonged survivalAssociated with better survival outcomesPatients treated with FOLFIRINOXCombination of 5-fluorouracilControlled TrialsIncidence of adverse eventsBetter survival outcomesCombination therapy groupNovel combination therapiesFirst-line treatmentHedgehog pathway inhibitorsSevere adverse eventsSerious adverse eventsTreatment of patientsReview of randomized controlled trialsSystematic review of randomized controlled trialsEnhance treatment of patients
2012
Single institution experience with FOLFIRINOX in advanced pancreatic cancer (PC).
Gunturu K, Thumar J, Hochster H, Stein S, Yao X, Cong X, Lacy J. Single institution experience with FOLFIRINOX in advanced pancreatic cancer (PC). Journal Of Clinical Oncology 2012, 30: e14534-e14534. DOI: 10.1200/jco.2012.30.15_suppl.e14534.Peer-Reviewed Original ResearchAdvanced pancreatic cancerMetastatic pancreatic cancerPancreatic cancerOverall survivalMetastatic PCProphylactic pegfilgrastimAdvanced unresectable pancreatic cancerECOG PS 0/1Efficacy of FOLFIRINOXGrade 3/4 fatigueUnresectable pancreatic cancerYale Cancer CenterSingle institution experienceKaplan-Meier methodWarrants further evaluationDose attenuationChemotherapy 5PS 0/1Free survivalSurgical resectionUnacceptable toxicityImproved tolerabilityPhysician's discretionRetrospective reviewInstitution experience
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