2024
Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer
Cecchini M, Salem R, Robert M, Czerniak S, Blaha O, Zelterman D, Rajaei M, Townsend J, Cai G, Chowdhury S, Yugawa D, Tseng R, Arbelaez C, Jiao J, Shroyer K, Thumar J, Kortmansky J, Zaheer W, Fischbach N, Persico J, Stein S, Khan S, Cha C, Billingsley K, Kunstman J, Johung K, Wiess C, Muzumdar M, Spickard E, Aushev V, Laliotis G, Jurdi A, Liu M, Escobar-Hoyos L, Lacy J. Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer. JAMA Oncology 2024, 10: 1027-1035. PMID: 38900452, PMCID: PMC11190830, DOI: 10.1001/jamaoncol.2024.1575.Peer-Reviewed Original ResearchProgression-free survivalPancreatic ductal adenocarcinomaOverall survivalCtDNA levelsPhase 2 nonrandomized controlled trialAnalysis of circulating tumor DNAMedian progression-free survivalResectable pancreatic ductal adenocarcinomaControlled trialsAssess surgical candidacyBaseline ctDNA levelModified 5-fluorouracilResectable pancreatic cancerPancreatic protocol computed tomographyAssociated with recurrenceTumor molecular featuresAggressive malignant tumorKaplan-Meier estimatesRandomized clinical trialsStandard of careCtDNA-positivePreoperative cyclesNonrandomized controlled trialsUnresectable diseaseModified FOLFIRINOX
2023
Pre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer
Peters G, Talcott W, Peters N, Dhanasopan A, Lacy J, Cecchini M, Kortmansky J, Stein S, Lattanzi S, Park H, Boffa D, Johung K, Jethwa K. Pre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer. Journal Of Gastrointestinal Oncology 2023, 14: 1181-1192. PMID: 37435226, PMCID: PMC10331751, DOI: 10.21037/jgo-22-1005.Peer-Reviewed Original ResearchProgression-free survivalMedian progression-free survivalOverall survivalIC-CRTInduction chemotherapySingle-institution retrospective cohort studyPre-operative chemoradiotherapyAdvanced esophageal cancerAdvanced esophageal carcinomaPathologic complete responseRetrospective cohort studyKaplan-Meier methodSubset of patientsProportional hazards regressionCycles of inductionAdenocarcinoma histologyCRT cohortCohort studyComplete responsePathologic responseTreatment cohortsDistant metastasisHazards regressionEsophageal cancerEsophageal carcinoma
2020
A phase 1b expansion study of TAS‐102 with oxaliplatin for refractory metastatic colorectal cancer
Cecchini M, Kortmansky JS, Cui C, Wei W, Thumar JR, Uboha NV, Hafez N, Lacy J, Fischbach NA, Sabbath KD, Gomez CM, Sporn JR, Stein S, Hochster HS. A phase 1b expansion study of TAS‐102 with oxaliplatin for refractory metastatic colorectal cancer. Cancer 2020, 127: 1417-1424. PMID: 33351187, PMCID: PMC8085021, DOI: 10.1002/cncr.33379.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsDrug Administration ScheduleDrug CombinationsDrug Resistance, NeoplasmFemaleFluorouracilHumansIrinotecanLeucovorinMaleMiddle AgedOrganoplatinum CompoundsOxaliplatinProgression-Free SurvivalPyrrolidinesResponse Evaluation Criteria in Solid TumorsThymineTrifluridineConceptsMetastatic colorectal cancerOverall response rateRefractory metastatic colorectal cancerProgression-free survivalTAS-102Colorectal cancerDay 1Primary endpointOverall survivalDose escalationDay 5Median progression-free survivalPhase 1b studyMedian overall survivalResponse Evaluation CriteriaTreat populationDose expansionPartial responseStandard dosesUnexpected side effectsStudy treatmentTumor shrinkageUnexpected toxicitiesSide effectsNovel antimetaboliteA Single-Institution Experience of Induction 5-Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin Followed by Surgery Versus Consolidative Radiation for Borderline and Locally Advanced Unresectable Pancreatic Cancer.
Cecchini M, Miccio JA, Pahade J, Lacy J, Salem RR, Johnson SB, Blakaj A, Stein S, Kortmansky JS, Johung KL. A Single-Institution Experience of Induction 5-Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin Followed by Surgery Versus Consolidative Radiation for Borderline and Locally Advanced Unresectable Pancreatic Cancer. Pancreas 2020, 49: 904-911. PMID: 32658074, DOI: 10.1097/mpa.0000000000001592.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaLA PDACUnresectable pancreatic ductal adenocarcinomaInduction FOLFIRINOXConsolidative radiotherapyOverall survivalAdvanced unresectable pancreatic ductal adenocarcinomaSingle-center retrospective reviewMeaningful survival benefitMedian overall survivalUnresectable pancreatic cancerR0 resection rateKaplan-Meier methodSingle institution experienceBenefits of surgeryLog-rank testConsolidative radiationDefinitive radiationLA patientsPreoperative radiationResection rateSurgery patientsSurvival benefitSurvival impactImproved survival
2019
Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial
Eng C, Kim T, Bendell J, Argilés G, Tebbutt N, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal N, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F, Investigators I, Ahn J, Asselah J, Badarinath S, Baijal S, Begbie S, Berry S, Canon J, Carbone R, Cervantes A, Cha Y, Chang K, Chaudhry A, Chmielowska E, Cho S, Chu D, Couture F, Cultrera J, Cunningham D, Van Cutsem E, Cuyle P, Davies J, Dowden S, Dvorkin M, Ganju V, Garcia R, Kerr R, Kim T, King K, Kortmansky J, Kozloff M, Lam K, Lee J, Lee A, Lesperance B, Luppi G, Ma B, Maiello E, Mandanas R, Marshall J, Marx G, Mullamitha S, Nechaeva M, Park J, Pavlakis N, Ponce C, Potemski P, Raouf S, Reeves J, Segal N, Siena S, Smolin A, Streb J, Strickland A, Szutowicz-Zielinska E, Tabernero J, Tan B, Valera J, Van den Eynde M, Vergauwe P, Vickers M, Womack M, Wroblewska M, Young R. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. The Lancet Oncology 2019, 20: 849-861. PMID: 31003911, DOI: 10.1016/s1470-2045(19)30027-0.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerMicrosatellite-stable metastatic colorectal cancerRegorafenib groupOverall survivalColorectal cancerAdverse eventsCombination groupAtezolizumab groupAtezolizumab monotherapyOpen-labelBaseline Eastern Cooperative Oncology Group performance statusEndpoint of improving overall survivalEastern Cooperative Oncology Group performance statusAll-cause grade 3Increased blood creatine phosphokinaseTreat metastatic colorectal cancerIntention-to-treat populationControlled trialsSafety of atezolizumabSystemic chemotherapy regimensThird-line settingMedian overall survivalTreatment-related deathsImmunotherapy to patientsMedian follow-upPhase 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
A phase IB/II randomized study of mFOLFIRINOX (mFFOX) + pegylated recombinant human hyaluronidase (PEGPH20) versus mFFOX alone in patients with good performance status metastatic pancreatic adenocarcinoma (mPC): SWOG S1313 (NCT #01959139).
Ramanathan R, McDonough S, Philip P, Hingorani S, Lacy J, Kortmansky J, Thumar J, Chiorean E, Shields A, Behl D, Mehan P, Gaur R, Seery T, Guthrie K, Hochster H. A phase IB/II randomized study of mFOLFIRINOX (mFFOX) + pegylated recombinant human hyaluronidase (PEGPH20) versus mFFOX alone in patients with good performance status metastatic pancreatic adenocarcinoma (mPC): SWOG S1313 (NCT #01959139). Journal Of Clinical Oncology 2018, 36: 208-208. DOI: 10.1200/jco.2018.36.4_suppl.208.Peer-Reviewed Original ResearchMetastatic pancreatic adenocarcinomaPhase II studyOverall survivalII studyPhase Ib/IIProphylactic growth factor supportUntreated metastatic pancreatic adenocarcinomaRandomized phase II studyGemcitabine/nab-paclitaxelAdequate organ functionMedian overall survivalGrowth factor supportInterim futility analysisRecombinant human hyaluronidaseClinical trial informationDelivery of gemcitabineBolus 5FULMWH prophylaxisMedian OSTumor hyaluronanCombination armNab-paclitaxelPrimary endpointThromboembolic eventsStandard arm
2017
Phase II Study of Modified FOLFOX6 With Bevacizumab in Metastatic Gastroesophageal Adenocarcinoma
Li J, Yao X, Kortmansky JS, Fischbach NA, Stein S, Deng Y, Zhang Y, Doddamane I, Karimeddini D, Hochster HS, Lacy J. Phase II Study of Modified FOLFOX6 With Bevacizumab in Metastatic Gastroesophageal Adenocarcinoma. American Journal Of Clinical Oncology 2017, 40: 146-151. PMID: 25144267, DOI: 10.1097/coc.0000000000000114.Peer-Reviewed Original ResearchConceptsMetastatic gastroesophageal adenocarcinomaProgression-free survivalGastroesophageal adenocarcinomaOverall survivalTreatment-related grade 3/4 toxicityResponse rateMedian progression-free survivalProspective phase II trialLonger progression-free survivalCisplatin-based regimensConfirmed response rateEfficacy of bevacizumabFirst-line bevacizumabOxaliplatin-based regimenUntreated metastatic adenocarcinomaGrade 3/4 toxicitiesMedian overall survivalAddition of bevacizumabPhase II studyPhase II trialModified FOLFOX6GI perforationHemorrhagic eventsII trialII study
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 tomographyPatients
2013
Phase II study of mFOLFOX with bevacizumab (Bev) in metastatic gastroesophageal and gastric (GE) adenocarcinoma (AC).
Li J, Kortmansky J, Fischbach N, Stein S, Yao X, Hochster H, Lacy J. Phase II study of mFOLFOX with bevacizumab (Bev) in metastatic gastroesophageal and gastric (GE) adenocarcinoma (AC). Journal Of Clinical Oncology 2013, 31: 4084-4084. DOI: 10.1200/jco.2013.31.15_suppl.4084.Peer-Reviewed Original ResearchCisplatin-based regimensOverall survivalGE adenocarcinomaResponse rateMetastatic sitesProspective phase II trialECOG PS 0/1Grade 3/4 toxicitiesMedian overall survivalPhase II studyPhase II trialPhase III studyDVT/PELiver 19Median TTPPrior gastrectomyPS 0/1GI perforationHemorrhagic eventsII studyII trialIII studyMedian survivalMedian ageGastric adenocarcinoma
2007
A phase I study of erlotinib in combination with gemcitabine and radiation in locally advanced, non-operable pancreatic adenocarcinoma
Duffy A, Kortmansky J, Schwartz G, Capanu M, Puleio S, Minsky B, Saltz L, O’Reilly E, Kelsen D. A phase I study of erlotinib in combination with gemcitabine and radiation in locally advanced, non-operable pancreatic adenocarcinoma. Annals Of Oncology 2007, 19: 86-91. PMID: 17878176, DOI: 10.1093/annonc/mdm441.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsCombined Modality TherapyDeoxycytidineDisease ProgressionErlotinib HydrochlorideFemaleGemcitabineHumansMaleMaximum Tolerated DoseMiddle AgedNeutropeniaPancreatic NeoplasmsProtein Kinase InhibitorsQuinazolinesRadiotherapy, AdjuvantSurvival AnalysisThrombocytopeniaTreatment OutcomeConceptsDose level 1Radiation therapyDaily erlotinibAdvanced pancreas cancerDose level 2Dose of erlotinibGemcitabine-based chemoradiationMTD of erlotinibAdvanced pancreatic cancerElevated liver enzymesPartial response rateDose-limiting toxicityPoor prognostic cancerDose delaysDose gemcitabineGemcitabine 1000Stable diseaseWeekly gemcitabineMedian survivalOverall survivalAdditional patientsPancreas cancerPancreatic cancerPancreatic adenocarcinomaLiver enzymes
2006
A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas
Duran I, Kortmansky J, Singh D, Hirte H, Kocha W, Goss G, Le L, Oza A, Nicklee T, Ho J, Birle D, Pond G, Arboine D, Dancey J, Aviel-Ronen S, Tsao M, Hedley D, Siu L. A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. British Journal Of Cancer 2006, 95: 1148-1154. PMID: 17031397, PMCID: PMC2360568, DOI: 10.1038/sj.bjc.6603419.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsCarcinoid TumorCarcinoma, NeuroendocrineDisease ProgressionExanthemaFatigueFemaleFollow-Up StudiesHumansHyperglycemiaInfusions, IntravenousMaleMiddle AgedPancreatic NeoplasmsPhosphorylationProtein KinasesProto-Oncogene Proteins c-aktRibosomal Protein S6SirolimusSurvival AnalysisTOR Serine-Threonine KinasesTreatment OutcomeConceptsAdvanced neuroendocrine carcinomaNeuroendocrine carcinomaAdverse eventsOverall survivalFrequent drug-related adverse eventsDrug-related adverse eventsRash/desquamationTreat response ratePhase II studyPercentage of patientsHigher baseline levelsII studyWeekly dosesNeuroendocrine tumorsTumor responsePharmacodynamic analysisPharmacodynamic studiesTumor biopsiesTemsirolimusResponse rateBaseline levelsPatientsPathway downregulationArchival specimensPhosphorylation of S6