2024
Phase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes
Sundar R, Chia D, Zhao J, Lee A, Kim G, Tan H, Pang A, Shabbir A, Willaert W, Ma H, Huang K, Hagihara T, Tan A, Ong C, Wong J, Seo C, Walsh R, Chan G, Cheo S, Soh C, Callebout E, Geboes K, Ng M, Lum J, Leow W, Selvarajan S, Hoorens A, Ang W, Pang H, Tan P, Yong W, Chia C, Ceelen W, So J. Phase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes. ESMO Open 2024, 9: 103681. PMID: 39288528, PMCID: PMC11421236, DOI: 10.1016/j.esmoop.2024.103681.Peer-Reviewed Original ResearchConceptsGastric cancer peritoneal metastasisPeritoneal cancer indexNivolumab combinationPeritoneal metastasisPeritoneal tumorsNaive CD8+ T cellsCD8+ central memoryEnhanced T cell infiltrationTreatment-related adverse eventsCD8+ T cellsGrade 4 vomitingRegression grade 1First-in-human trialImmune checkpoint inhibitionMemory CD4+T cell infiltrationImmunogenic cell deathSystemic immunotherapyCheckpoint inhibitionSystemic therapyCancer indexCD4+Intraperitoneal treatmentT cellsAdverse events
2022
Outcomes of a Phase II Study of Intraperitoneal Paclitaxel Plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases
Chia D, Sundar R, Kim G, Ang J, Shabbir A, So J, Yong W. Outcomes of a Phase II Study of Intraperitoneal Paclitaxel Plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 30: 1889-1890. PMID: 36564654, DOI: 10.1245/s10434-022-12877-3.Peer-Reviewed Original ResearchTargeting OCT2 with Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neurotoxicity
Nepal M, Taheri H, Li Y, Talebi Z, Uddin M, Jin Y, DiGiacomo D, Gibson A, Lustberg M, Hu S, Sparreboom A. Targeting OCT2 with Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neurotoxicity. Cancer Research Communications 2022, 2: 1334-1343. PMID: 36506732, PMCID: PMC9730833, DOI: 10.1158/2767-9764.crc-22-0172.Peer-Reviewed Original ResearchConceptsDRG neuronsPeripheral neurotoxicitySide effectsOxaliplatin-induced peripheral neurotoxicityOxaliplatin-based regimensOxaliplatin-based treatmentPharmacokinetics of oxaliplatinEffect of duloxetineMouse DRG neuronsWild-type miceCytotoxicity of oxaliplatinConcentration-dependent mannerColorectal cancerCancer patientsPlasma levelsOIPNPlasma pharmacokineticsDuloxetinePrevention strategiesTherapeutic candidateOxaliplatinTumor cell linesTranslational feasibilityMiceComplete protectionOutcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases
Chia D, Sundar R, Kim G, Ang J, Lum J, Nga M, Goh G, Seet J, Chee C, Tan H, Ho J, Ngoi N, Lee M, Muthu V, Chan G, Pang A, Ang Y, Choo J, Lim J, Teh J, Lwin A, Soon Y, Shabbir A, So J, Yong W. Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 29: 8597-8605. PMID: 36070113, DOI: 10.1245/s10434-022-11998-z.Peer-Reviewed Original ResearchConceptsGastric cancer peritoneal metastasisIP-PTXConversion surgeryIntraperitoneal paclitaxelMedian OSSystemic chemotherapyPeritoneal metastasisSC groupConversion to negative cytologyResultsThe median OSProgression-free survivalPhase II studyMethodsForty-four patientsIntravenous oxaliplatinMedian PFSOral capecitabineSystemic capecitabineExtraperitoneal metastasesNegative cytologyPeritoneal diseaseOverall survivalPerformance statusPrimary endpointSecondary endpointsIP cohortThe phenotype and value of nerve conduction studies in measuring chemotherapy-induced peripheral neuropathy: A secondary analysis of pooled data
Wang M, Bandla A, Sundar R, Molassiotis A. The phenotype and value of nerve conduction studies in measuring chemotherapy-induced peripheral neuropathy: A secondary analysis of pooled data. European Journal Of Oncology Nursing 2022, 60: 102196. PMID: 36067640, DOI: 10.1016/j.ejon.2022.102196.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyMeasuring chemotherapy-induced peripheral neuropathyNerve conduction studiesQuality of lifePeripheral neuropathySecondary analysisSecondary analysis of pooled dataPerformance of nerve conduction studiesNerve conduction study resultsNerve conduction study parametersTime points of assessmentInitiation of chemotherapyPatient-reported symptomsOxaliplatin-based chemotherapyPooled dataClinical examination outcomeAnalysis of pooled dataConduction studiesCIPN assessmentMonitoring peripheral neuropathyNeurotoxic chemotherapyProspective studyClinical examinationSensory nervesChemotherapyTime-Dependent Studies of Oxaliplatin and Other Nucleolar Stress-Inducing Pt(II) Derivatives
Pigg H, Yglesias M, Sutton E, McDevitt C, Shaw M, DeRose V. Time-Dependent Studies of Oxaliplatin and Other Nucleolar Stress-Inducing Pt(II) Derivatives. ACS Chemical Biology 2022, 17: 2262-2271. PMID: 35917257, DOI: 10.1021/acschembio.2c00399.Peer-Reviewed Original ResearchConceptsNucleolar stressStress inductionHigh overall degreeSpecific cellular responsesRibosome biogenesisRRNA transcriptionConformation showCellular responsesCell deathDNA damageKey intermolecular interactionsH drug treatmentMechanistic understandingCellular accumulationSmall moleculesDNA adduct formationInductionBiogenesisTranscriptionStressInhibitionAdduct formationInteractionPotential explanationConformationDownregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer
Li Y, Gan Y, Liu J, Li J, Zhou Z, Tian R, Sun R, Liu J, Xiao Q, Li Y, Lu P, Peng Y, Peng Y, Shu G, Yin G. Downregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer. Signal Transduction And Targeted Therapy 2022, 7: 87. PMID: 35351858, PMCID: PMC8964798, DOI: 10.1038/s41392-022-00902-6.Peer-Reviewed Original ResearchConceptsOxaliplatin resistanceColorectal cancerTumor growthMEIS1 expressionCell sensitivity to oxaliplatinPreventing DNA damage repairCombination of oxaliplatinSurvival of CRC patientsTreatment of colorectal cancerSensitivity to oxaliplatinEZH2 inhibitor GSK126Suppressed tumor growthReverse oxaliplatin resistanceFrontline treatmentAcquired ResistanceCRC patientsInhibitor GSK126OxaliplatinFEN1 expressionTherapeutic strategiesDNA damage repairELFN1-AS1Cell survivalMeis1Patients
2021
Randomized Phase II Study of PET Response–Adapted Combined Modality Therapy for Esophageal Cancer: Mature Results of the CALGB 80803 (Alliance) Trial
Goodman KA, Ou FS, Hall NC, Bekaii-Saab T, Fruth B, Twohy E, Meyers MO, Boffa DJ, Mitchell K, Frankel WL, Niedzwiecki D, Noonan A, Janjigian YY, Thurmes PJ, Venook AP, Meyerhardt JA, O'Reilly EM, Ilson DH. Randomized Phase II Study of PET Response–Adapted Combined Modality Therapy for Esophageal Cancer: Mature Results of the CALGB 80803 (Alliance) Trial. Journal Of Clinical Oncology 2021, 39: 2803-2815. PMID: 34077237, PMCID: PMC8407649, DOI: 10.1200/jco.20.03611.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarboplatinChemoradiotherapyCombined Modality TherapyEsophageal NeoplasmsFemaleFluorodeoxyglucose F18FluorouracilFollow-Up StudiesHumansLeucovorinMaleMiddle AgedOxaliplatinPositron-Emission TomographyPrognosisRadiopharmaceuticalsSurvival RateYoung AdultConceptsPositron emission tomographyRepeat positron emission tomographyPET respondersEsophagogastric junction adenocarcinomaStandardized uptake valueInduction FOLFOXPET nonrespondersPCR rateOverall survivalJunction adenocarcinomaPathologic complete response rateRandomized phase II studyBaseline positron emission tomographyMaximum standardized uptake valueInduction chemotherapy regimenComplete response rateEarly response assessmentMedian overall survivalPhase II studyPrimary end pointCombined modality therapySame chemotherapyChemotherapy regimenEligible patientsII studyEarly nucleolar responses differentiate mechanisms of cell death induced by oxaliplatin and cisplatin
Sutton EC, DeRose VJ. Early nucleolar responses differentiate mechanisms of cell death induced by oxaliplatin and cisplatin. Journal Of Biological Chemistry 2021, 296: 100633. PMID: 33819479, PMCID: PMC8131322, DOI: 10.1016/j.jbc.2021.100633.Peer-Reviewed Original Research
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 antimetaboliteLaparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry
Arjona-Sanchez A, Aziz O, Passot G, Salti G, Esquivel J, Van der Speeten K, Piso P, Nedelcut D, Sommariva A, Yonemura Y, Turaga K, Selvasekar C, Rodriguez-Ortiz L, Sanchez-Hidalgo J, Casado-Adam A, Rufian-Peña S, Briceño J, Glehen O. Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry. European Journal Of Surgical Oncology 2020, 47: 1420-1426. PMID: 33298341, DOI: 10.1016/j.ejso.2020.11.140.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCisplatinColonic NeoplasmsCytoreduction Surgical ProceduresDisease-Free SurvivalDoxorubicinFemaleFollow-Up StudiesHumansHyperthermic Intraperitoneal ChemotherapyLaparoscopyLength of StayMaleMesotheliomaMiddle AgedMitomycinNeoadjuvant TherapyNeoplasm, ResidualOvarian NeoplasmsOxaliplatinPaclitaxelPeritoneal NeoplasmsPseudomyxoma PeritoneiRegistriesSeverity of Illness IndexSurvival RateTumor BurdenConceptsPeritoneal Surface Oncology Group InternationalHyperthermic intraperitoneal chemotherapyLength of stayCytoreductive surgeryIntraperitoneal chemotherapyPeritoneal metastasisBenign multicystic mesotheliomaLaparoscopic cytoreductive surgeryLimited peritoneal metastasesPost-operative morbidityFree of diseaseMedian length of stayIndividual patient dataMedian PCIPeritoneal diseasePeritoneal disseminationMulticystic mesotheliomaOvarian carcinomaMidterm outcomesPseudomyxoma peritoneiLaparoscopic approachPostoperative outcomesFrequent indicationInvasive histologyColon carcinomaPIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases
Kim G, Tan L, Sundar R, Lieske B, Chee C, Ho J, Shabbir A, Babak M, Ang W, Goh B, Yong W, Wang L, So J. PIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases. Clinical Cancer Research 2020, 27: 1875-1881. PMID: 33148667, DOI: 10.1158/1078-0432.ccr-20-2152.Peer-Reviewed Original ResearchConceptsPressurized intraperitoneal aerosol chemotherapyPressurized intraperitoneal aerosolized chemotherapy proceduresPeritoneal cancer indexPeritoneal metastasisAerosol chemotherapyMedian peritoneal cancer indexPeritoneal Regression Grading ScoreRecommended phase II doseGrade 2 pancreatitisHighest-dose cohortPhase II doseDose-limiting toxicityFirst-line chemotherapyDose-escalation designTreat peritoneal metastasisPhase I studyImprove drug distributionII doseStable diseaseCancer indexMedian ageCohort expansionGastrointestinal tumorsPharmacokinetic analysisDose levelsNeuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice
Huang KM, Leblanc AF, Uddin ME, Kim JY, Chen M, Eisenmann ED, Gibson A, Li Y, Hong KW, DiGiacomo D, Xia S, Alberti P, Chiorazzi A, Housley SN, Cope TC, Sprowl JA, Wang J, Loprinzi CL, Noonan A, Lustberg M, Cavaletti G, Pabla N, Hu S, Sparreboom A. Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice. Journal Of Clinical Investigation 2020, 130: 4601-4606. PMID: 32484793, PMCID: PMC7456253, DOI: 10.1172/jci136796.Peer-Reviewed Original ResearchConceptsOrganic cation transporter 2Peripheral neurotoxicityColorectal cancerOxaliplatin-induced peripheral neurotoxicityOxaliplatin-containing therapyOxaliplatin-induced neurotoxicitySatellite glial cellsOxaliplatin neurotoxicityChronic formCancer patientsGlial cellsPreclinical modelsPreventive strategiesMouse modelPharmacological approachesPharmacological targetingTranslational significanceNeurotoxicityTransporter 2PatientsUptake transportersCancerAnticancer drugsCandidate transportersSolute carriersHIPEC with cisplatin in a patient with a prior hypersensitivity reaction to systemic oxaliplatin
Morgan R, Parsad S, Turaga K, Eng O. HIPEC with cisplatin in a patient with a prior hypersensitivity reaction to systemic oxaliplatin. Basic & Clinical Pharmacology & Toxicology 2020, 127: 551-553. PMID: 32623784, DOI: 10.1111/bcpt.13464.Peer-Reviewed Original ResearchConceptsHyperthermic intraperitoneal chemotherapyHypersensitivity reactionsSystemic oxaliplatinDiscontinued due to toxicityPlatinum-based chemotherapeutic agentsAlternative routes of administrationPlatinum-based agentsRoute of administrationIntraperitoneal chemotherapySystemic therapyDesensitization protocolCross-reactivityCase reportChemotherapeutic agentsSkin testPatientsCisplatinTherapyOxaliplatinAdverse effectsSafety parametersHypersensitivityPlatinum saltsDesensitizationAgentsA 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 survivalEvaluation of the Association of Perioperative UGT1A1 Genotype–Dosed gFOLFIRINOX With Margin-Negative Resection Rates and Pathologic Response Grades Among Patients With Locally Advanced Gastroesophageal Adenocarcinoma
Catenacci D, Chase L, Lomnicki S, Karrison T, de Wilton Marsh R, Rampurwala M, Narula S, Alpert L, Setia N, Xiao S, Hart J, Siddiqui U, Peterson B, Moore K, Kipping-Johnson K, Markevicius U, Gordon B, Allen K, Racette C, Maron S, Liao C, Polite B, Kindler H, Turaga K, Prachand V, Roggin K, Ferguson M, Posner M. Evaluation of the Association of Perioperative UGT1A1 Genotype–Dosed gFOLFIRINOX With Margin-Negative Resection Rates and Pathologic Response Grades Among Patients With Locally Advanced Gastroesophageal Adenocarcinoma. JAMA Network Open 2020, 3: e1921290. PMID: 32058557, DOI: 10.1001/jamanetworkopen.2019.21290.Peer-Reviewed Original ResearchConceptsLocally advanced gastroesophageal adenocarcinomaPathological response gradeAdvanced gastroesophageal adenocarcinomaGastroesophageal adenocarcinomaResection rateMargin-negativeResponse gradeMargin-negative resection rateMedian disease-free survivalUGT1A1 genotype groupsMedian overall survivalLocally advanced adenocarcinomaHigher adverse eventsR0 resection rateDisease-free survivalCoprimary end pointsPhase 2 trialRate of recurrenceIntestinal-type tumorsR0 resectionR1 resectionAdvanced adenocarcinomaNeoadjuvant chemotherapyPerioperative therapyOverall survivalNeurological safety of oxaliplatin in patients with uncommon variants in Charcot-Marie-tooth disease genes
Le-Rademacher J, Lopez C, Kanwar R, Major-Elechi B, Abyzov A, Banck M, Therneau T, Sloan J, Loprinzi C, Beutler A. Neurological safety of oxaliplatin in patients with uncommon variants in Charcot-Marie-tooth disease genes. Journal Of The Neurological Sciences 2020, 411: 116687. PMID: 32018185, PMCID: PMC7096263, DOI: 10.1016/j.jns.2020.116687.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyRisk of CIPNTooth disease (CMT) genesCIPN riskCharcot-MariePatient-reported outcome instrumentsSingle nucleotide variantsFavor of casesNeurological safetyCommon genetic testsNeurotoxic chemotherapyOxaliplatin therapyPeripheral neuropathyChemotherapy decisionsClinical guidanceOutcome instrumentsUncommon variantPatientsNon-synonymous single nucleotide variantsSignificant associationOxaliplatinGenetic testsRiskCommon single nucleotide variantsCMT
2019
Randomized, Phase II Study Prospectively Evaluating Treatment of Metastatic Esophageal, Gastric, or Gastroesophageal Cancer by Gene Expression of ERCC1: SWOG S1201.
Iqbal S, McDonough S, Lenz HJ, Ilson D, Burtness B, Nangia CS, Barzi A, Schneider CJ, Liu JJ, Dotan E, Guthrie KA, Hochster HS. Randomized, Phase II Study Prospectively Evaluating Treatment of Metastatic Esophageal, Gastric, or Gastroesophageal Cancer by Gene Expression of ERCC1: SWOG S1201. Journal Of Clinical Oncology 2019, 38: 472-479. PMID: 31815582, PMCID: PMC7007287, DOI: 10.1200/jco.19.00925.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsDNA-Binding ProteinsEndonucleasesEsophageal NeoplasmsEsophagogastric JunctionFemaleFluorouracilGene ExpressionHumansLeucovorinMaleMiddle AgedNeoplasm MetastasisOrganoplatinum CompoundsOxaliplatinPrognosisProgression-Free SurvivalProportional Hazards ModelsProspective StudiesStomach NeoplasmsYoung AdultConceptsProgression-free survivalAdvanced esophagogastric cancerPhase II studyPlatinum-based therapyOverall survivalII studySuperior median progression-free survivalMedian progression-free survivalMRNA expressionRegimen of irinotecanUpper GI tumorsZubrod performance statusPercent of patientsOccurrence of gradeStandard of careMetastatic esophagealEsophagogastric cancerPerformance statusUntreated patientsGastroesophageal cancerGI tumorsTreatment armsFOLFOXPlatinum sensitivityPatientsNucleolar Stress Induction by Oxaliplatin and Derivatives
Sutton EC, McDevitt CE, Prochnau JY, Yglesias MV, Mroz AM, Yang MC, Cunningham RM, Hendon CH, DeRose VJ. Nucleolar Stress Induction by Oxaliplatin and Derivatives. Journal Of The American Chemical Society 2019, 141: 18411-18415. PMID: 31670961, PMCID: PMC7735645, DOI: 10.1021/jacs.9b10319.Peer-Reviewed Original ResearchMonofunctional platinum(II) compounds and nucleolar stress: is phenanthriplatin unique?
McDevitt CE, Yglesias MV, Mroz AM, Sutton EC, Yang MC, Hendon CH, DeRose VJ. Monofunctional platinum(II) compounds and nucleolar stress: is phenanthriplatin unique? JBIC Journal Of Biological Inorganic Chemistry 2019, 24: 899-908. PMID: 31494760, PMCID: PMC7660985, DOI: 10.1007/s00775-019-01707-9.Peer-Reviewed Original Research
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