2022
Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211)
Kunz PL, Graham NT, Catalano PJ, Nimeiri HS, Fisher GA, Longacre TA, Suarez CJ, Martin BA, Yao JC, Kulke MH, Hendifar AE, Shanks JC, Shah MH, Zalupski MM, Schmulbach EL, Reidy-Lagunes DL, Strosberg JR, O'Dwyer PJ, O'Dwyer P, Benson A. Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211). Journal Of Clinical Oncology 2022, 41: 1359-1369. PMID: 36260828, PMCID: PMC9995105, DOI: 10.1200/jco.22.01013.Peer-Reviewed Original ResearchConceptsAdvanced pancreatic neuroendocrine tumorsProgression-free survivalPancreatic neuroendocrine tumorsMedian progression-free survivalPrimary end pointNeuroendocrine tumorsResponse rateObjective responseOverall survivalRandomized studyIntermediate-grade pancreatic neuroendocrine tumorsLonger progression-free survivalEnd pointMGMT deficiencyMedian overall survivalPrimary analysis populationKey eligibility criteriaPhase II trialSmall prospective studiesHigh response rateMethylguanine methyltransferaseCapecitabine/Eligible patientsSecondary endpointsII trial
2020
Patient Selection and Toxicities of PRRT for Metastatic Neuroendocrine Tumors and Research Opportunities
Shaheen S, Moradi F, Gamino G, Kunz PL. Patient Selection and Toxicities of PRRT for Metastatic Neuroendocrine Tumors and Research Opportunities. Current Treatment Options In Oncology 2020, 21: 25. PMID: 32172368, DOI: 10.1007/s11864-020-0711-9.Peer-Reviewed Original ResearchConceptsPeptide receptor radionuclide therapySomatostatin analoguesToxicity of PRRTOpinion statementNeuroendocrine tumorsMetastatic neuroendocrine tumorsLandscape of treatmentReceptor radionuclide therapyRecent treatment advancesTreatment of NETsPatient selectionNeuroendocrine tumorsTreatment advancesSomatostatin receptorsMinimal response rateRadionuclide therapyResponse rateHeterogenous groupTherapyTumor cellsBiological hallmarksTumorsTreatmentNETsIndolentNeoplasmsTime to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Phase III Studies in Carcinoid Syndrome
Dillon JS, Kulke MH, Hörsch D, Anthony LB, Warner RRP, Bergsland E, Welin S, O’Dorisio T, Kunz PL, McKee C, Lapuerta P, Banks P, Pavel M. Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Phase III Studies in Carcinoid Syndrome. Journal Of Gastrointestinal Cancer 2020, 52: 212-221. PMID: 32146619, PMCID: PMC7714089, DOI: 10.1007/s12029-020-00375-2.Peer-Reviewed Original ResearchConceptsCarcinoid syndrome diarrheaBM frequencyPhase III studyTelotristat ethylBowel movementsCarcinoid syndromeIII studySomatostatin analoguesDouble-blind treatment periodBowel movement frequencyMajority of patientsLog-rank testCox regression modelTime of onsetPlacebo TIDHazard ratioPrespecified analysisMedian timeSustained responseTreatment periodSustained reductionPatientsConsecutive weeksTELESTARSurvival analysis methodsImpact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study
Strosberg J, Kunz PL, Hendifar A, Yao J, Bushnell D, Kulke MH, Baum RP, Caplin M, Ruszniewski P, Delpassand E, Hobday T, Verslype C, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Paganelli G, Severi S, Morse M, Metz DC, Ansquer C, Courbon F, Al-Nahhas A, Baudin E, Giammarile F, Taïeb D, Mittra E, Wolin E, O’Dorisio T, Lebtahi R, Deroose CM, Grana CM, Bodei L, Öberg K, Polack BD, He B, Mariani MF, Gericke G, Santoro P, Erion JL, Ravasi L, Krenning E. Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study. European Journal Of Nuclear Medicine And Molecular Imaging 2020, 47: 2372-2382. PMID: 32123969, PMCID: PMC7396396, DOI: 10.1007/s00259-020-04709-x.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseHumansLiver NeoplasmsNeuroendocrine TumorsOctreotideOrganometallic CompoundsTreatment OutcomeConceptsLiver tumor burdenProgression-free survivalLargest target lesionHigher liver tumour burdenTumor burdenMidgut neuroendocrine tumorsAlkaline phosphatase elevationNeuroendocrine tumorsTarget lesionsLesion sizeHazard ratioTreatment outcomesAnalysis of PFSHigh-dose octreotide LARMedian progression-free survivalImproved progression-free survivalNETTER-1 studyNETTER-1 trialLiver function abnormalitiesKaplan-Meier estimatesOctreotide LARPrimary endpointFunction abnormalitiesBaseline factorsCox regression
2018
Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome
Weickert MO, Kaltsas G, Hörsch D, Lapuerta P, Pavel M, Valle JW, Caplin ME, Bergsland E, Kunz PL, Anthony LB, Grande E, Öberg K, Welin S, Lombard-Bohas C, Ramage JK, Kittur A, Yang QM, Kulke MH. Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome. Clinical Therapeutics 2018, 40: 952-962.e2. PMID: 29724499, DOI: 10.1016/j.clinthera.2018.04.006.Peer-Reviewed Original ResearchConceptsMetastatic neuroendocrine tumorsTelotristat ethylCarcinoid syndromePlacebo TIDWeek 12Neuroendocrine tumorsMetabolic parametersNutritional statusDouble-blind treatment periodWeight gainWeight lossUncontrolled carcinoid syndromeSomatostatin analogue therapyBowel movement frequencyStatistical analysis planOverall nutritional statusAnalogue therapyDiarrhea severityTreatment periodPatientsSyndromeWeight changeAnalysis planMovement frequencyTumorsTelotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial
Pavel M, Gross DJ, Benavent M, Perros P, Srirajaskanthan R, Warner RRP, Kulke MH, Anthony LB, Kunz PL, Hörsch D, Weickert MO, Lapuerta P, Jiang W, Kassler-Taub K, Wason S, Fleming R, Fleming D, Garcia-Carbonero R. Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial. Endocrine Related Cancer 2018, 25: 309-322. PMID: 29330194, PMCID: PMC5811631, DOI: 10.1530/erc-17-0455.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsOpen-label extensionCarcinoid syndromeTelotristat ethylSomatostatin analoguesWeek 12Rates of TEAEsDouble-blind treatment periodPhase 3 trialTryptophan hydroxylase inhibitorMedian treatment differencesCS diarrheaBowel movementsEfficacy endpointAdverse eventsPrimary safetyTreatment periodHydroxylase inhibitorPatientsSerious eventsPercent changeTreatment differencesPlaceboEfficacySignificant reduction
2017
Understanding the Patient Experience with Carcinoid Syndrome: Exit Interviews from a Randomized, Placebo-controlled Study of Telotristat Ethyl
Anthony L, Ervin C, Lapuerta P, Kulke MH, Kunz P, Bergsland E, Hörsch D, Metz DC, Pasieka J, Pavlakis N, Pavel M, Caplin M, Öberg K, Ramage J, Evans E, Yang QM, Jackson S, Arnold K, Law L, DiBenedetti DB. Understanding the Patient Experience with Carcinoid Syndrome: Exit Interviews from a Randomized, Placebo-controlled Study of Telotristat Ethyl. Clinical Therapeutics 2017, 39: 2158-2168. PMID: 29074312, DOI: 10.1016/j.clinthera.2017.09.013.Peer-Reviewed Original ResearchMeSH KeywordsDiarrheaDouble-Blind MethodFemaleHumansMaleMalignant Carcinoid SyndromeMiddle AgedPhenylalaninePyrimidinesTreatment OutcomeConceptsTelotristat ethylBM frequencyCarcinoid syndromeBowel movementsPatient experienceDouble-blind treatment periodCarcinoid syndrome symptomsPrimary end pointSomatostatin analogue therapyPhase III studyClinical trial experienceTryptophan hydroxylase inhibitorEligible patientsStudy drugAnalogue therapyIII studyPatient interviewsResponder analysisTreatment periodPatient reportsSyndrome symptomsTreatment responsePrespecified criteriaHydroxylase inhibitorPatientsThe North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors
Strosberg JR, Halfdanarson TR, Bellizzi AM, Chan JA, Dillon JS, Heaney AP, Kunz PL, O’Dorisio T, Salem R, Segelov E, Howe JR, Pommier RF, Brendtro K, Bashir MA, Singh S, Soulen MC, Tang L, Zacks JS, Yao JC, Bergsland EK. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors. Pancreas 2017, 46: 707-714. PMID: 28609356, PMCID: PMC5642985, DOI: 10.1097/mpa.0000000000000850.Peer-Reviewed Original ResearchConceptsMidgut neuroendocrine tumorsNeuroendocrine tumorsNorth American Neuroendocrine Tumor Society Consensus GuidelinesNorth American Neuroendocrine Tumor SocietyNETTER-1 trialRADIANT-4 studyRefractory carcinoid syndromePhase 3 studyNonfunctioning neuroendocrine tumorEnteropancreatic neuroendocrine tumorsConsensus-based guidelinesCLARINET trialRADIANT-2Carcinoid syndromeTelotristat ethylMedical managementTherapeutic optionsConsensus guidelinesSurgical guidelinesLu-DOTATATEMultidisciplinary panelProximal colonGastrointestinal tractSmall intestinePatients
2016
Neuroendocrine tumors of the pancreas: Degree of cystic component predicts prognosis
Cloyd JM, Kopecky KE, Norton JA, Kunz PL, Fisher GA, Visser BC, Dua MM, Park WG, Poultsides GA. Neuroendocrine tumors of the pancreas: Degree of cystic component predicts prognosis. Surgery 2016, 160: 708-713. PMID: 27216830, DOI: 10.1016/j.surg.2016.04.005.Peer-Reviewed Original ResearchConceptsCystic pancreatic neuroendocrine tumorsPancreatic neuroendocrine tumorsRecurrence-free survivalNeuroendocrine tumorsCystic tumorCystic componentSolid tumorsTumor sizeSingle academic medical centerMost pancreatic neuroendocrine tumorsFavorable clinicopathologic featuresSynchronous liver metastasesLymph node positivityLymph node metastasisTotal tumor sizeHigh gradeCross-sectional imagingAcademic medical centerSynchronous liverImmediate resectionLiver metastasesMetastatic diseaseNode positivityOperative resectionClinicopathologic characteristicsRole of Somatostatin Analogues in the Treatment of Neuroendocrine Tumors
Narayanan S, Kunz PL. Role of Somatostatin Analogues in the Treatment of Neuroendocrine Tumors. Hematology/Oncology Clinics Of North America 2016, 30: 163-177. PMID: 26614375, DOI: 10.1016/j.hoc.2015.09.008.Peer-Reviewed Original ResearchConceptsSomatostatin analoguesNeuroendocrine tumorsRole of SSAsTreatment of NETsPeptide receptor radionuclide therapyMetastatic neuroendocrine tumorsHormone-related symptomsReceptor radionuclide therapyRare epithelial neoplasmLocal therapySymptom managementTumor controlNeuroendocrine differentiationEffective therapyEpithelial neoplasmsDisease CenterPromising treatmentRadionuclide therapyTumor growthTherapyTreatmentTumorsSurgeryNeoplasmsLung
2015
Carcinoid and Neuroendocrine Tumors: Building on Success
Kunz PL. Carcinoid and Neuroendocrine Tumors: Building on Success. Journal Of Clinical Oncology 2015, 33: 1855-1863. PMID: 25918282, DOI: 10.1200/jco.2014.60.2532.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoid TumorCell DifferentiationChemoembolization, TherapeuticChemotherapy, AdjuvantHumansNeoplasm StagingNeuroendocrine TumorsPatient SelectionPrecision MedicinePredictive Value of TestsRadiopharmaceuticalsTreatment OutcomeRole of somatostatin analogues in the treatment of neuroendocrine tumors.
Narayanan S, Kunz PL. Role of somatostatin analogues in the treatment of neuroendocrine tumors. Journal Of The National Comprehensive Cancer Network 2015, 13: 109-17; quiz 117. PMID: 25583773, DOI: 10.6004/jnccn.2015.0012.Peer-Reviewed Original ResearchConceptsNeuroendocrine tumorsSomatostatin analoguesTumor controlTreatment of NETsSystemic tumor controlHormone-related symptomsManagement of patientsRare epithelial neoplasmAdvanced diseaseHormone excessSymptom managementNeuroendocrine differentiationEpithelial neoplasmsGastrointestinal tractPatientsTumorsTreatmentDiarrheaNeoplasmsLungSerotoninSyndromeSymptomsManagementMainstay
2014
Single- versus Multifraction Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma: Outcomes and Toxicity
Pollom EL, Alagappan M, von Eyben R, Kunz PL, Fisher GA, Ford JA, Poultsides GA, Visser BC, Norton JA, Kamaya A, Cox VL, Columbo LA, Koong AC, Chang DT. Single- versus Multifraction Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma: Outcomes and Toxicity. International Journal Of Radiation Oncology • Biology • Physics 2014, 90: 918-925. PMID: 25585785, DOI: 10.1016/j.ijrobp.2014.06.066.Peer-Reviewed Original ResearchConceptsStereotactic body radiation therapyCumulative incidence rateSingle-fraction groupUnresectable pancreatic adenocarcinomaBody radiation therapyPancreatic adenocarcinomaToxicity gradeSurvival rateLocal recurrenceIncidence rateRadiation therapySingle-fraction stereotactic body radiation therapyGastrointestinal toxicity gradeMajority of patientsGastrointestinal toxicityMedian survivalWorse survivalIndependent predictorsPancreatic cancerLocal controlPatientsAdenocarcinomaRecurrenceTherapyMonths
2013
Pancreatic neuroendocrine tumours: hypoenhancement on arterial phase computed tomography predicts biological aggressiveness
Worhunsky DJ, Krampitz GW, Poullos PD, Visser BC, Kunz PL, Fisher GA, Norton JA, Poultsides GA. Pancreatic neuroendocrine tumours: hypoenhancement on arterial phase computed tomography predicts biological aggressiveness. Hepato Pancreato Biliary 2013, 16: 304-311. PMID: 23991643, PMCID: PMC3967881, DOI: 10.1111/hpb.12139.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCell DifferentiationChi-Square DistributionFemaleHumansKaplan-Meier EstimateMaleMiddle AgedMultivariate AnalysisNeuroendocrine TumorsPancreatectomyPancreatic NeoplasmsPredictive Value of TestsProportional Hazards ModelsRetrospective StudiesRisk FactorsTime FactorsTomography, X-Ray ComputedTreatment OutcomeConceptsPancreatic neuroendocrine tumorsOverall survivalArterial phasePre-operative decisionsSynchronous liver metastasesWorse overall survivalMultidisciplinary treatmentSurgical resectionIndependent predictorsLiver metastasesLymph nodesPoor outcomePrognostic significanceClinicopathological variablesNeuroendocrine tumorsCT appearancePancreatic adenocarcinomaBiological aggressivenessTumor enhancementMultivariate analysisTumorsHypoenhancementIntermediate gradeResectionPatientsPhase II Study Evaluating 2 Dosing Schedules of Oral Foretinib (GSK1363089), cMET/VEGFR2 Inhibitor, in Patients with Metastatic Gastric Cancer
Shah MA, Wainberg ZA, Catenacci DV, Hochster HS, Ford J, Kunz P, Lee FC, Kallender H, Cecchi F, Rabe DC, Keer H, Martin AM, Liu Y, Gagnon R, Bonate P, Liu L, Gilmer T, Bottaro DP. Phase II Study Evaluating 2 Dosing Schedules of Oral Foretinib (GSK1363089), cMET/VEGFR2 Inhibitor, in Patients with Metastatic Gastric Cancer. PLOS ONE 2013, 8: e54014. PMID: 23516391, PMCID: PMC3597709, DOI: 10.1371/journal.pone.0054014.Peer-Reviewed Original ResearchConceptsObjective response rateMetastatic gastric cancerStable diseaseMET amplificationPhospho-METGastric adenocarcinomaIntermittent dosingGastric cancerTreatment-related adverse eventsPhase II studyMetastatic gastric adenocarcinomaRates of hypertensionElevated aspartate aminotransferaseOral multikinase inhibitorEndothelial cell growth factorVascular endothelial cell growth factorCell growth factorEvaluable patientsForetinib treatmentPrior therapyAdverse eventsII studyUnselected patientsDosing schedulesMedian age
2012
Neoadjuvant imatinib for borderline resectable GIST.
Koontz MZ, Visser BM, Kunz PL. Neoadjuvant imatinib for borderline resectable GIST. Journal Of The National Comprehensive Cancer Network 2012, 10: 1477-82; quiz 1482. PMID: 23221786, DOI: 10.6004/jnccn.2012.0154.Peer-Reviewed Original ResearchConceptsGastrointestinal stromal tumorsNeoadjuvant imatinibNeoadjuvant tyrosine kinase-inhibitor therapyResectable gastrointestinal stromal tumorsTyrosine kinase inhibitor therapyBorderline resectable tumorsCommon bile ductSuperior mesenteric veinKinase inhibitor therapyOptimal imaging modalityViable treatment strategySpindle cell neoplasmResectable tumorsRed blood cellsUpper endoscopyBlack stoolInhibitor therapyBile ductMedical oncologyStromal tumorsEmergency departmentCase reportMesenteric veinCell neoplasmsTreatment strategiesSeventh Edition (2010) of the AJCC/UICC Staging System for Gastric Adenocarcinoma: Is there Room for Improvement?
Patel MI, Rhoads KF, Ma Y, Ford JM, Visser BC, Kunz PL, Fisher GA, Chang DT, Koong A, Norton JA, Poultsides GA. Seventh Edition (2010) of the AJCC/UICC Staging System for Gastric Adenocarcinoma: Is there Room for Improvement? Annals Of Surgical Oncology 2012, 20: 1631-1638. PMID: 23149854, DOI: 10.1245/s10434-012-2724-5.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdolescentAdultAgedAged, 80 and overCaliforniaChemotherapy, AdjuvantFemaleGastrectomyHumansKaplan-Meier EstimateLymphatic MetastasisMaleMiddle AgedNeoplasm StagingProportional Hazards ModelsRadiotherapy, AdjuvantRetrospective StudiesStomach NeoplasmsTreatment OutcomeYoung AdultConceptsAJCC/UICC staging systemUICC staging systemStaging systemStage IBLymph nodesGastric adenocarcinomaAJCC/UICC stageAJCC/UICC systemCurative-intent surgical resectionSeventh editionKaplan-Meier methodOverall survival probabilityStatewide Health PlanningCancer registry dataNew grouping systemAdjuvant chemotherapyAdjuvant radiotherapySurgical resectionMedian ageUICC stageAsian patientsDischarge abstractsMedian numberRegistry dataGastric cancerCapecitabine-Induced Chest Pain Relieved by Diltiazem
Ambrosy AP, Kunz PL, Fisher GA, Witteles RM. Capecitabine-Induced Chest Pain Relieved by Diltiazem. The American Journal Of Cardiology 2012, 110: 1623-1626. PMID: 22939579, DOI: 10.1016/j.amjcard.2012.07.026.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAntimetabolites, AntineoplasticAnus NeoplasmsCalcium Channel BlockersCapecitabineCarcinoma, Squamous CellChest PainColorectal NeoplasmsCoronary VasospasmDeoxycytidineDiltiazemElectrocardiographyFemaleFluorouracilFollow-Up StudiesHumansMaleMiddle AgedProdrugsSecondary PreventionTreatment OutcomeConceptsChest painAcute ST-segment elevation myocardial infarctionST-segment elevation myocardial infarctionAnal squamous cell carcinomaSignificant coronary artery diseaseDiscontinuation of capecitabineElevation myocardial infarctionCoronary artery diseasePrimary colorectal adenocarcinomaSquamous cell carcinomaIschemia evaluationSecondary prophylaxisTroponin elevationArtery diseaseInitial presentationSustained reliefElectrocardiographic findingsCell carcinomaMyocardial infarctionColorectal adenocarcinomaPainPatientsChemotherapeutic agentsNovel management strategiesCapecitabinePhase I trial of ixabepilone administered as three oral doses each separated by 6 hours every 3 weeks in patients with advanced solid tumors
Kunz PL, He AR, Colevas AD, Pishvaian MJ, Hwang JJ, Clemens PL, Messina M, Kaleta R, Abrahao F, Sikic BI, Marshall JL. Phase I trial of ixabepilone administered as three oral doses each separated by 6 hours every 3 weeks in patients with advanced solid tumors. Investigational New Drugs 2012, 30: 2364-2370. PMID: 22331549, PMCID: PMC3703248, DOI: 10.1007/s10637-012-9800-3.Peer-Reviewed Original ResearchConceptsNeutropenic sepsisGrade 4 febrile neutropeniaDoses of ixabepiloneAdvanced solid tumorsExcellent performance statusPhase I trialSerial plasma samplesPlasma drug concentrationsRefractory advanced cancersHigh inter-individual variabilityFebrile neutropeniaPerformance statusI trialMedian ageAdvanced cancerInter-individual variabilityOral dosesSafety profileCohort 2Cohort 1Cohort 3PK variabilityOral formulationIxabepilonePatients
2010
Comparison of intensity‐modulated radiotherapy and 3‐dimensional conformal radiotherapy as adjuvant therapy for gastric cancer
Minn AY, Hsu A, La T, Kunz P, Fisher GA, Ford JM, Norton JA, Visser B, Goodman KA, Koong AC, Chang DT. Comparison of intensity‐modulated radiotherapy and 3‐dimensional conformal radiotherapy as adjuvant therapy for gastric cancer. Cancer 2010, 116: 3943-3952. PMID: 20564136, DOI: 10.1002/cncr.25246.Peer-Reviewed Original ResearchConceptsIntensity-modulated radiotherapyCRT groupGastric cancerConformal radiotherapyIMRT patientsAcute gastrointestinal toxicityMedian radiation doseMedian serum creatinineGastroesophageal junction cancerOverall survival rateConcurrent chemotherapyKidney V20Liver V30Median liverRecent creatinineAdjuvant chemoradiotherapyAdjuvant therapyGastrointestinal toxicityIMRT groupLocoregional failurePostoperative chemoradiotherapyJunction cancerRenal functionSerum creatinineTreatment breaks