2024
Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial
Choueiri T, Kuzel T, Tykodi S, Verzoni E, Kluger H, Nair S, Perets R, George S, Gurney H, Pachynski R, Folefac E, Castonguay V, Lee C, Vaishampayan U, Miller W, Bhagavatheeswaran P, Wang Y, Gupta S, DeSilva H, Lee C, Escudier B, Motzer R. Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial. ESMO Open 2024, 9: 104073. PMID: 39642635, PMCID: PMC11667034, DOI: 10.1016/j.esmoop.2024.104073.Peer-Reviewed Original ResearchConceptsAdvanced renal cell carcinomaNivolumab + ipilimumabProgression-free survivalDuration of responseMedian duration of responseProgression-free survival ratesProgrammed death-ligand 1Renal cell carcinomaImmuno-oncologyOpen-labelCell carcinomaPatients treated with nivolumabTyrosine kinase inhibitor therapyTreatment-related adverse eventsLymphocyte activation gene-3Death-ligand 1Kinase inhibitor therapyAssessment of combination therapyEffective combination regimenImmuno-oncology studiesCombination regimenInhibitor therapyLAG-3Combination therapySecondary endpointsProof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid
Papini C, Ullah I, Ranjan A, Zhang S, Wu Q, Spasov K, Zhang C, Mothes W, Crawford J, Lindenbach B, Uchil P, Kumar P, Jorgensen W, Anderson K. Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2320713121. PMID: 38621119, PMCID: PMC11046628, DOI: 10.1073/pnas.2320713121.Peer-Reviewed Original ResearchConceptsDirect-acting antiviralsSARS-CoV-2Lack of off-target effectsIn vitro pharmacological profileTreatment of patientsDevelopment of severe symptomsPharmacological propertiesDrug-drug interactionsSARS-CoV-2 infectionProof-of-concept studySARS-CoV-2 M<sup>pro</sup>.Combination regimenImmunocompromised patientsLead compoundsSARS-CoV-2 main proteaseOral doseActive drugTreat infectionsPharmacological profileSARS-CoV-2 MPotential preclinical candidateOff-target effectsPatientsComplete recoveryCapsule formulation
2023
MicroRNAs with Multiple Targets of Immune Checkpoints, as a Potential Sensitizer for Immune Checkpoint Inhibitors in Breast Cancer Treatment
Zhou H, Jia W, Lu L, Han R. MicroRNAs with Multiple Targets of Immune Checkpoints, as a Potential Sensitizer for Immune Checkpoint Inhibitors in Breast Cancer Treatment. Cancers 2023, 15: 824. PMID: 36765782, PMCID: PMC9913694, DOI: 10.3390/cancers15030824.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsImmune checkpoint blockadeBreast cancerCheckpoint inhibitorsCheckpoint moleculesImmune checkpointsImmune checkpoint moleculesCancer-associated mortalityBreast cancer treatmentCommon cancer typesCombination regimenAdverse eventsCheckpoint blockadeClinical benefitTherapeutic effectTherapeutic candidateTherapeutic potentialCancer typesCancerCancer treatmentApplication of miRNAsTargetScan databaseMiRNA therapyTreatmentInhibitorsPhase Ib study of HSP90 inhibitor, onalespib (AT13387), in combination with paclitaxel in patients with advanced triple-negative breast cancer
Williams N, Quiroga D, Johnson C, Brufsky A, Chambers M, Bhattacharya S, Patterson M, Sardesai S, Stover D, Lustberg M, Noonan A, Cherian M, Bystry D, Hill K, Chen M, Phelps M, Grever M, Stephens J, Ramaswamy B, Carson W, Wesolowski R. Phase Ib study of HSP90 inhibitor, onalespib (AT13387), in combination with paclitaxel in patients with advanced triple-negative breast cancer. Therapeutic Advances In Medical Oncology 2023, 15: 17588359231217976. PMID: 38152697, PMCID: PMC10752118, DOI: 10.1177/17588359231217976.Peer-Reviewed Original ResearchAdvanced triple-negative breast cancerTriple-negative breast cancerProgression-free survivalDuration of responseOverall response ratePrior taxane therapyAdverse eventsTaxane therapyCombination therapyBreast cancerMedian DORMedian progression-free survivalNon-hematologic adverse eventsPhase Ib studyPhase Ib trialPhase II doseAcceptable toxicity profileDose-limiting toxicityDrug interaction profileIb trialIntravenous paclitaxelPaclitaxel efficacyExpansion cohortCombination regimenMetastatic disease
2022
Emerging Role of PARP Inhibitors in Metastatic Prostate Cancer
Unlu S, Kim JW. Emerging Role of PARP Inhibitors in Metastatic Prostate Cancer. Current Oncology Reports 2022, 24: 1619-1631. PMID: 35931885, DOI: 10.1007/s11912-022-01305-0.Peer-Reviewed Original ResearchConceptsPARP inhibitorsBRCA2 mutationsProstate cancerFDA approvalMetastatic prostate cancer patientsAccelerated FDA approvalDeleterious BRCA2 mutationsHRR gene mutationsObjective response ratePhase II studyMetastatic prostate cancerProstate cancer patientsPoly (ADP-ribose) polymerase (PARP) inhibitorsUS FDA approvalSomatic mutationsMCRPC patientsCombination regimenII studyClinical benefitRadium-223Cancer patientsStandard treatmentAndrogen receptorDNA damage repair pathwaysClinical developmentAnalysis of Dual Combination Therapies Used in Treatment of Hypertension in a Multinational Cohort
Lu Y, Van Zandt M, Liu Y, Li J, Wang X, Chen Y, Chen Z, Cho J, Dorajoo SR, Feng M, Hsu MH, Hsu JC, Iqbal U, Jonnagaddala J, Li YC, Liaw ST, Lim HS, Ngiam KY, Nguyen PA, Park RW, Pratt N, Reich C, Rhee SY, Sathappan SMK, Shin SJ, Tan HX, You SC, Zhang X, Krumholz HM, Suchard MA, Xu H. Analysis of Dual Combination Therapies Used in Treatment of Hypertension in a Multinational Cohort. JAMA Network Open 2022, 5: e223877. PMID: 35323951, PMCID: PMC8948532, DOI: 10.1001/jamanetworkopen.2022.3877.Peer-Reviewed Original ResearchConceptsDual combination therapyUse of ACEIAntihypertensive drug classesProportion of patientsKhoo Teck Puat HospitalCombination therapyUniversity Hospital databaseHospital databaseDrug classesDual combinationSouth Western Sydney Local Health DistrictWestern Sydney Local Health DistrictPatients age 65 yearsSydney Local Health DistrictElectronic health record databasePatients age 18Local Health DistrictAge 65 yearsTreatment of hypertensionHealth record databaseARB monotherapyTreatment escalationAdult patientsCohort studyCombination regimen
2019
174O Predictive and prognostic value of B-cell gene-expression signatures and B-cell receptor (BCR) repertoire in HER2+ breast cancer: A correlative analysis of the CALGB 40601 clinical trial (Alliance)
Fernandez-Martinez A, Tanioka M, Fan C, Parker J, Hoadley K, Krop I, Partridge A, Carey L, Perou C. 174O Predictive and prognostic value of B-cell gene-expression signatures and B-cell receptor (BCR) repertoire in HER2+ breast cancer: A correlative analysis of the CALGB 40601 clinical trial (Alliance). Annals Of Oncology 2019, 30: v55. DOI: 10.1093/annonc/mdz240.Peer-Reviewed Original ResearchPathologic complete responseEvent-free survivalGene expression signaturesPrognostic valueBreast cancerCALGB 40601Clinical trialsSignature scoreImmune-mediated anti-tumor responseHigher pathologic complete responseTumor-infiltrating lymphocyte densityNeoadjuvant treatment strategiesAnti-tumor responseB cell signaturesB cell receptor repertoireExpression signaturesImmune-related signaturePre-treatment samplesDual HER2Neoadjuvant studiesCombination regimenComplete responseLymphocyte densityClinical parametersUnivariate analysisCombinatorial drug screening of mammary cells with induced mesenchymal transformation to identify drug combinations for triple-negative breast cancer
Colavito SA, Platt JT, Held MA, Liu Z, Sokup R, Stern DF. Combinatorial drug screening of mammary cells with induced mesenchymal transformation to identify drug combinations for triple-negative breast cancer. Oncotarget 2019, 10: 4822-4839. PMID: 31448050, PMCID: PMC6690678, DOI: 10.18632/oncotarget.27104.Peer-Reviewed Original ResearchBreast cancerDrug combinationsB-cell lymphoma-2 inhibitorTriple-negative breast cancerEffective treatment strategiesBreast cancer cellsEffective drug combinationsCombination regimenPoor prognosisCombination therapyTreatment optionsTreatment strategiesBCL2 inhibitorsEffective treatmentSelf-renewal capabilityCancerTumor cellsDifferent dosesCancer cellsMammary cellsCheckpoint kinase 1 inhibitorsKinase 1 inhibitorMesenchymal characteristicsMesenchymal transformationUntreated cells
2018
RARE-24. OBJECTIVE RESPONSE AND CLINICAL BENEFIT IN RECURRENT EPENDYMOMA IN ADULTS: FINAL REPORT OF CERN 08-02: A PHASE II STUDY OF DOSE-DENSE TEMOZOLOMIDE AND LAPATINIB
Armstrong T, Yuan Y, Wu J, Mendoza T, Vera E, Omuro A, Lieberman F, Robins H, Gerstner E, Wu J, Wen P, Mikkelsen T, Aldape K, Gilbert M. RARE-24. OBJECTIVE RESPONSE AND CLINICAL BENEFIT IN RECURRENT EPENDYMOMA IN ADULTS: FINAL REPORT OF CERN 08-02: A PHASE II STUDY OF DOSE-DENSE TEMOZOLOMIDE AND LAPATINIB. Neuro-Oncology 2018, 20: vi241-vi241. PMCID: PMC6217700, DOI: 10.1093/neuonc/noy148.998.Peer-Reviewed Original ResearchDose-dense temozolomideObjective responseClinical benefitRecurrent ependymomaAdult clinical trialsModerate-severe painStable disease rateStandard salvage regimenPhase II studyRole of chemotherapyProgression-free survivalDisease-related symptomsDaily lapatinibMedian KPSMedian PFSPFS ratesPrior relapseSalvage regimenAutonomic dysfunctionFree survivalPrimary endpointRecurrent diseaseAdult patientsCombination regimenII studyPrior Medications and the Cardiovascular Benefits From Combination Angiotensin‐Converting Enzyme Inhibition Plus Calcium Channel Blockade Among High‐Risk Hypertensive Patients
Brook RD, Kaciroti N, Bakris G, Dahlöf B, Pitt B, Velazquez E, Weber M, Zappe DH, Hau T, Jamerson KA. Prior Medications and the Cardiovascular Benefits From Combination Angiotensin‐Converting Enzyme Inhibition Plus Calcium Channel Blockade Among High‐Risk Hypertensive Patients. Journal Of The American Heart Association 2018, 7: e006940. PMID: 29301757, PMCID: PMC5778960, DOI: 10.1161/jaha.117.006940.Peer-Reviewed Original ResearchMeSH KeywordsAgedAmlodipineAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsBenzazepinesBlood PressureCalcium Channel BlockersCause of DeathDrug Therapy, CombinationFemaleHumansHydrochlorothiazideHypertensionMaleMiddle AgedRandomized Controlled Trials as TopicRisk AssessmentRisk FactorsSodium Chloride Symporter InhibitorsTime FactorsTreatment OutcomeConceptsHigh-risk hypertensive patientsCardiovascular risk reductionHypertensive patientsAntihypertensive regimenCombination therapyBlood pressure control statusGreater cardiovascular risk reductionRenin-angiotensin system blockadeAngiotensin-converting enzyme inhibitorPrimary composite eventsPrior antihypertensive therapyPrimary composite outcomeCalcium channel blockadeLipid-lowering medicationsPrior medication useCalcium channel blockersRisk reductionACCOMPLISH trialAntihypertensive therapySystem blockadeCardiovascular benefitsCombination regimenComposite outcomeDrug regimensMedication use
2017
Phase I Trial of Triapine–Cisplatin–Paclitaxel Chemotherapy for Advanced Stage or Metastatic Solid Tumor Cancers
Kunos CA, Chu E, Makower D, Kaubisch A, Sznol M, Ivy SP. Phase I Trial of Triapine–Cisplatin–Paclitaxel Chemotherapy for Advanced Stage or Metastatic Solid Tumor Cancers. Frontiers In Oncology 2017, 7: 62. PMID: 28421163, PMCID: PMC5378786, DOI: 10.3389/fonc.2017.00062.Peer-Reviewed Original ResearchCombination regimenSolid tumor cancersI trialTumor cancersAdvanced stageRecurrent uterine cervix cancerCommon grade 3Phase II trialProgression-free survivalPhase I trialContinuous intravenous infusionUterine cervix cancerStable diseaseElectrolyte abnormalitiesII trialObjective responsePaclitaxel chemotherapyReversible anemiaIntravenous infusionMonths durationCervix cancerGrade 3Day 1Day 3Regimen
2016
Drug interactions between buprenorphine, methadone and hepatitis C therapeutics
Ogbuagu O, Friedland G, Bruce RD. Drug interactions between buprenorphine, methadone and hepatitis C therapeutics. Expert Opinion On Drug Metabolism & Toxicology 2016, 12: 721-731. PMID: 27140427, DOI: 10.1080/17425255.2016.1183644.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDirect acting antiviralsOpioid use disorderDrug interactionsUse disordersHCV direct acting antiviralsNovel direct acting antiviralsHepatitis C virus infectionHepatitis C therapeuticsHigh HCV prevalenceC virus infectionMedication-Assisted TherapyPharmacodynamic drug interactionsSpecific drug combinationsDrug package insertsHCV prevalenceHCV infectionHCV treatmentOpioid withdrawalActing antiviralsCombination regimenPharmacodynamic assessmentConcurrent administrationDrug levelsHigh prevalenceVirus infection
2012
Phase I trial of the combination of flavopiridol and imatinib mesylate in patients with Bcr-Abl+ hematological malignancies
Bose P, Perkins EB, Honeycut C, Wellons MD, Stefan T, Jacobberger JW, Kontopodis E, Beumer JH, Egorin MJ, Imamura CK, Douglas Figg W, Karp JE, Koc ON, Cooper BW, Luger SM, Colevas AD, Roberts JD, Grant S. Phase I trial of the combination of flavopiridol and imatinib mesylate in patients with Bcr-Abl+ hematological malignancies. Cancer Chemotherapy And Pharmacology 2012, 69: 1657-1667. PMID: 22349810, PMCID: PMC3365614, DOI: 10.1007/s00280-012-1839-5.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsCombination of flavopiridolStable diseasePhase I dose-escalation studyPhiladelphia chromosome-positive acute leukemiaSecond-generation BCR-ABL tyrosine kinase inhibitorBone marrow blast countI dose-escalation studyBCR-ABL tyrosine kinase inhibitorsKinase inhibitorsImatinib-resistant diseaseIntravenous infusion weeklyPhase II dosesDose-escalation studyMarrow blast countPhase I trialNovel combination regimenMajor pharmacokinetic interactionsBCR-ABL tyrosine kinaseChronic myelogenous leukemiaInfusion weeklyCyclin-dependent kinase inhibitorBlast countCombination regimenComplete response
2004
Phase I Study of the Farnesyltransferase Inhibitor Lonafarnib with Paclitaxel in Solid Tumors
Khuri FR, Glisson BS, Kim ES, Statkevich P, Thall PF, Meyers ML, Herbst RS, Munden RF, Tendler C, Zhu Y, Bangert S, Thompson E, Lu C, Wang XM, Shin DM, Kies MS, Papadimitrakopoulou V, Fossella FV, Kirschmeier P, Bishop WR, Hong WK. Phase I Study of the Farnesyltransferase Inhibitor Lonafarnib with Paclitaxel in Solid Tumors. Clinical Cancer Research 2004, 10: 2968-2976. PMID: 15131032, DOI: 10.1158/1078-0432.ccr-03-0412.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerGrade 4 diarrheaCell lung cancerPartial responseLung cancerMetastatic non-small cell lung cancerSolid tumorsGrade 3 peripheral neuropathyPrincipal grade 3/4 toxicitiesDose level 3Durable partial responseGrade 3 hyperbilirubinemiaPrevious taxane therapyGrade 3/4 toxicitiesGrade 4 neutropeniaPhase II trialDose-limiting toxicityPhase I trialFarnesyltransferase inhibitor lonafarnibNovel farnesyltransferase inhibitorPlasma paclitaxelII trialTaxane therapyCombination regimenMedian durationTreatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon &agr;2b and ribavirin: an open-label series1
Rodriguez-Luna H, Khatib A, Sharma P, De Petris G, Williams JW, Ortiz J, Hansen K, Mulligan D, Moss A, Douglas DD, Balan V, Rakela J, Vargas HE. Treatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon &agr;2b and ribavirin: an open-label series1. Transplantation 2004, 77: 190-194. PMID: 14742979, DOI: 10.1097/01.tp.0000100481.14514.bb.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsDrug Therapy, CombinationFemaleHepacivirusHepatitis CHumansImmunosuppressive AgentsInterferon alpha-2Interferon-alphaLiver Function TestsLiver TransplantationMaleMiddle AgedPolyethylene GlycolsRecombinant ProteinsRecurrenceReverse Transcriptase Polymerase Chain ReactionRibavirinRNA, ViralTime FactorsTreatment OutcomeConceptsOrthotopic liver transplantationEnd of treatmentHCV recurrenceLiver transplantationPEG-IFNHepatitis C virus recurrenceRecurrent hepatitis C infectionDiscontinuation of therapyNecro-inflammatory scoreUndetectable viral loadHepatitis C infectionResponse 6 monthsBone marrow toxicityReverse transcriptase-polymerase chain reactionTranscriptase-polymerase chain reactionHistologic benefitRecurrent HCVVirologic clearanceC infectionVirologic responseVirus recurrenceAggressive managementCombination regimenViral clearanceViral response
2003
Targeting the epidermal growth factor receptor in non-small cell lung cancer.
Herbst RS, Bunn PA. Targeting the epidermal growth factor receptor in non-small cell lung cancer. Clinical Cancer Research 2003, 9: 5813-24. PMID: 14676101.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerEGFR-TK inhibitorsSystemic chemotherapyClinical trialsClinical developmentMetastatic non-small cell lung cancerTwo-drug combination regimenEpidermal growth factor receptor tyrosine kinase inhibitor gefitinibSingle-agent activityRate of deathNew treatment approachesKinase inhibitor gefitinibEpidermal growth factor receptorGrowth factor receptorCombination regimenDisease progressionPlatinum agentsTreatment approachesSolid tumorsTumor growthInhibitor gefitinibTherapyCancerA phase I/IIA trial of continuous five-day infusion of squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
Herbst RS, Hammond LA, Carbone DP, Tran HT, Holroyd KJ, Desai A, Williams JI, Bekele BN, Hait H, Allgood V, Solomon S, Schiller JH. A phase I/IIA trial of continuous five-day infusion of squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clinical Cancer Research 2003, 9: 4108-15. PMID: 14519633.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAngiogenesis InhibitorsAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCarcinoma, Non-Small-Cell LungCholestanolsDisease-Free SurvivalFemaleHumansInfusions, IntravenousLactatesLung NeoplasmsMaleMiddle AgedNeoplasm StagingPaclitaxelPatient SelectionPleural EffusionSurvival AnalysisTime FactorsConceptsNon-small cell lung cancerCell lung cancerLung cancerDay 1Continuous infusionChemotherapy-naive non-small cell lung cancerAdvanced non-small cell lung cancerPhase I/IIa studyPhase I/IIa trialPhase II doseDose-limiting toxicityPartial tumor responseFive-day infusionEffective therapeutic strategyPatient survival dataEvaluable patientsStable diseaseStage IIIBStarting doseClinical responseCombination regimenCytotoxic chemotherapyIIa studyIIa trialMedian survival
2002
Safety and pharmacokinetic effects of TNP-470, an angiogenesis inhibitor, combined with paclitaxel in patients with solid tumors: evidence for activity in non-small-cell lung cancer.
Herbst RS, Madden TL, Tran HT, Blumenschein GR, Meyers CA, Seabrooke LF, Khuri FR, Puduvalli VK, Allgood V, Fritsche HA, Hinton L, Newman RA, Crane EA, Fossella FV, Dordal M, Goodin T, Hong WK. Safety and pharmacokinetic effects of TNP-470, an angiogenesis inhibitor, combined with paclitaxel in patients with solid tumors: evidence for activity in non-small-cell lung cancer. Journal Of Clinical Oncology 2002, 20: 4440-7. PMID: 12431966, DOI: 10.1200/jco.2002.04.006.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAntibiotics, AntineoplasticAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCyclohexanesDrug Administration ScheduleFemaleHumansLung NeoplasmsMaleMiddle AgedO-(Chloroacetylcarbamoyl)fumagillolPaclitaxelSesquiterpenesTreatment OutcomeConceptsTNP-470Solid tumorsPharmacokinetic interactionsOptimal doseAntiangiogenic agent TNP-470Minimal pharmacokinetic interactionsNeuropsychiatric test resultsSingle-agent doseMaximum-tolerated doseDoses of paclitaxelCell lung cancerPaclitaxel dosePrior chemotherapyChemotherapy regimensCombination regimenMedian survivalPartial responseArm AArm BPaclitaxel clearanceTreatment armsCytotoxic therapyLung cancerPharmacokinetic effectsPreclinical studies
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