2022
Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial
Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. Journal Of Clinical Oncology 2022, 40: 968-977. PMID: 35007153, PMCID: PMC8937015, DOI: 10.1200/jco.21.02050.Peer-Reviewed Original ResearchConceptsProgression-free survivalUterine carcinosarcomaOvarian carcinosarcomaEligible patientsHazard ratioMore patientsPC armMedian progression-free survivalRandomized phase III trialNRG Oncology trialsPhase III trialsPI armsGenitourinary hemorrhageHematologic toxicityMedian OSIII trialsLonger OSStandard treatmentGreater death rateStage IIINoninferiority designOncology trialsPatientsStage IStage IV
2020
Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clinical Cancer Research 2020, 26: 3928-3935. PMID: 32601075, PMCID: PMC8792803, DOI: 10.1158/1078-0432.ccr-20-0953.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinChemotherapy, AdjuvantCystadenocarcinoma, SerousCytoreduction Surgical ProceduresDrug Administration ScheduleEndometrial NeoplasmsEndometriumFemaleFollow-Up StudiesHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPaclitaxelProgression-Free SurvivalReceptor, ErbB-2Survival AnalysisTrastuzumabConceptsProgression-free survivalRandomized phase II trialPhase II trialOverall survivalHER2/neuStage IIICarboplatin-paclitaxelII trialRecurrent diseaseControl armSurvival analysisRecurrent uterine serous carcinomaCarboplatin/paclitaxelUterine serous carcinomaOverall survival analysisEvaluable patientsEligible patientsPrimary endpointSecondary endpointsEndometrial cancerAggressive variantSerous carcinomaPrimary treatmentSurvival medianPatients
2018
Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer
Altwerger G, Florsheim EB, Menderes G, Black J, Schwab C, Gressel GM, Nelson WK, Carusillo N, Passante T, Huang G, Litkouhi B, Azodi M, Silasi DA, Santin A, Schwartz PE, Ratner ES. Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer. Journal Of Cancer Research And Clinical Oncology 2018, 144: 2449-2456. PMID: 30255380, DOI: 10.1007/s00432-018-2753-y.Peer-Reviewed Original ResearchConceptsCarboplatin hypersensitivityCarboplatin desensitizationHypersensitive patientsOverall survivalRisk factorsOvarian cancerTwo-sided Fisher exactAdvanced stage ovarian cancerInfusion of carboplatinRecurrent ovarian cancerIndependent risk factorLonger overall survivalStage ovarian cancerOvarian cancer patientsLong-term treatmentNew risk factorsHigher likelihoodTwo-sided p valueT-testStudent's t-testDesignRetrospective studyGermline BRCA1/2Improved OSLonger OSDesensitization protocolRandomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu.
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. Journal Of Clinical Oncology 2018, 36: 2044-2051. PMID: 29584549, DOI: 10.1200/jco.2017.76.5966.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Progression-free survivalUterine serous carcinomaRecurrent uterine serous carcinomaMedian progression-free survivalRandomized phase II trialEpidermal growth factor receptor 2Phase II trialGrowth factor receptor 2Serous carcinomaHER2/neuFactor receptor 2II trialTreatment armsReceptor 2Stage IIIHER2/neu-positive diseaseOne-sided log-rank testMethods Eligible patientsPrimary end pointPrimary stage IIIUnexpected safety signalsLog-rank testHumanized monoclonal antibodyEligible patients
2016
Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro
Bellone S, Bignotti E, Lonardi S, Ferrari F, Centritto F, Masserdotti A, Pettinella F, Black J, Menderes G, Altwerger G, Hui P, Lopez S, de Haydu C, Bonazzoli E, Predolini F, Zammataro L, Cocco E, Ferrari F, Ravaggi A, Romani C, Facchetti F, Sartori E, Odicino FE, Silasi DA, Litkouhi B, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro. Gynecologic Oncology 2016, 144: 146-152. PMID: 27894751, PMCID: PMC5183545, DOI: 10.1016/j.ygyno.2016.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCarcinomaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SurvivalDisease-Free SurvivalDNA Polymerase IIDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityMiddle AgedMutationPoly-ADP-Ribose Binding ProteinsTumor Cells, CulturedConceptsBetter prognosisTumor cell linesInfiltration of CD4Number of CD4Platinum-based chemotherapyT lymphocyte infiltrationPD-1 receptorCell linesLow metastatic capabilityPOLE-mutated tumorsWild-type ECsEC cell linesLymphocyte infiltrationFavorable prognosisPD-1EC patientsType tumorsEnhanced immunogenicityT lymphocytesMolecular subtypesTumors correlatesChemotherapyMetastatic capabilityPrognosisTumorsPlatinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study
Altwerger G, Gressel GM, English DP, Nelson WK, Carusillo N, Silasi DA, Azodi M, Santin A, Schwartz PE, Ratner ES. Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study. Gynecologic Oncology 2016, 144: 77-82. PMID: 27789084, DOI: 10.1016/j.ygyno.2016.09.027.Peer-Reviewed Original ResearchConceptsPositive skin testsHypersensitivity reactionsDesensitization protocolSkin testCarboplatin infusionLife-threatening hypersensitivity reactionSingle-institution retrospective studyCarboplatin desensitization protocolPrior hypersensitivity reactionMajority of patientsCarboplatin hypersensitivity reactionsCarboplatin hypersensitivityPulmonary hypertensionAdverse eventsRetrospective reviewRetrospective studyGynecologic cancerGrade 0Patient deathRisk factorsCardiac conditionsPatientsLarger studyInfusionAge
2013
Class III β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel
Roque DM, Buza N, Glasgow M, Bellone S, Bortolomai I, Gasparrini S, Cocco E, Ratner E, Silasi DA, Azodi M, Rutherford TJ, Schwartz PE, Santin AD. Class III β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel. Clinical & Experimental Metastasis 2013, 31: 101-110. PMID: 24005572, PMCID: PMC3947146, DOI: 10.1007/s10585-013-9614-5.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansImmunohistochemistryNeoadjuvant TherapyOvarian NeoplasmsPaclitaxelPrognosisReal-Time Polymerase Chain ReactionTubulinTumor MicroenvironmentUp-RegulationConceptsClass III β-tubulinIII β-tubulinClass III β-tubulin expressionNeoadjuvant chemotherapyPoor overall survivalOverall survivalΒ-tubulin expressionClass III β-tubulin overexpressionPrimary cytoreductionNeoadjuvant carboplatin/paclitaxelPoor median overall survivalTumor microenvironmentAdvanced ovarian carcinomaCarboplatin/paclitaxelMedian overall survivalOvarian cancer patientsCell linesCancer stem cellsNeoadjuvant carboplatinPrimary debulkingVitro chemosensitivityClinical outcomesPatient populationCancer patientsStromal expression
2012
Neoadjuvant chemotherapy (NACT) is an effective way of managing elderly women with advanced stage ovarian cancer (FIGO Stage IIIC and IV)
Glasgow MA, Yu H, Rutherford TJ, Azodi M, Silasi D, Santin AD, Schwartz PE. Neoadjuvant chemotherapy (NACT) is an effective way of managing elderly women with advanced stage ovarian cancer (FIGO Stage IIIC and IV). Journal Of Surgical Oncology 2012, 107: 195-200. PMID: 22648987, DOI: 10.1002/jso.23171.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCarcinoma, Ovarian EpithelialChemotherapy, AdjuvantCohort StudiesDrug Administration ScheduleFemaleHumansNeoadjuvant TherapyNeoplasm StagingNeoplasms, Glandular and EpithelialOvarian NeoplasmsPaclitaxelRetrospective StudiesSurvival AnalysisTreatment OutcomeConceptsEpithelial ovarian cancerAdvanced stage ovarian cancerUpfront cytoreductive surgeryNeoadjuvant chemotherapyStage ovarian cancerCytoreductive surgeryOvarian cancerNACT patientsAge 70Stage IV epithelial ovarian cancerAdvanced epithelial ovarian cancerImproved progression-free survivalRetrospective cohort studyShorter ICU stayStage IV diseaseProgression-free survivalLess blood lossSmall bowel resectionOverall survival analysisICU staySame chemotherapyUpfront surgeryMacroscopic diseasePerioperative morbidityStage IIIC
2011
A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer
Ratner ES, Keane FK, Lindner R, Tassi RA, Paranjape T, Glasgow M, Nallur S, Deng Y, Lu L, Steele L, Sand S, Muller RU, Bignotti E, Bellone S, Boeke M, Yao X, Pecorelli S, Ravaggi A, Katsaros D, Zelterman D, Cristea MC, Yu H, Rutherford TJ, Weitzel JN, Neuhausen SL, Schwartz PE, Slack FJ, Santin AD, Weidhaas JB. A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer. Oncogene 2011, 31: 4559-4566. PMID: 22139083, PMCID: PMC3342446, DOI: 10.1038/onc.2011.539.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBRCA1 ProteinBRCA2 ProteinCarboplatinCell Line, TumorCell SurvivalDrug Resistance, NeoplasmFemaleGenotypeHumansKaplan-Meier EstimateMiddle AgedMultivariate AnalysisMutationNeoplasms, Glandular and EpithelialOvarian NeoplasmsPaclitaxelPolymorphism, Single NucleotidePrognosisProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsRNA InterferenceTreatment OutcomeConceptsEpithelial ovarian cancerEOC patientsKRAS-variantOvarian cancerPoor outcomeCancer riskTumor biologyPlatinum resistanceComplete clinical dataBiomarkers of outcomeDirect targetingEOC cell growthKnown BRCA mutationsFuture treatment approachesSubset of tumorsPlatinum chemotherapy resistanceCell linesNeoadjuvant chemotherapyBRCA mutationsClinical dataTreatment approachesChemotherapy resistanceKRAS oncogeneMultivariate analysisPatients
2010
Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro
Cross SN, Cocco E, Bellone S, Anagnostou VK, Brower SL, Richter CE, Siegel ER, Schwartz PE, Rutherford TJ, Santin AD. Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro. American Journal Of Obstetrics And Gynecology 2010, 203: 162.e1-162.e8. PMID: 20417484, PMCID: PMC2918912, DOI: 10.1016/j.ajog.2010.02.056.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsApoptosisCarboplatinCell Line, TumorCell ProliferationCisplatinCystadenocarcinoma, PapillaryCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedProbabilityReceptor, ErbB-2Sensitivity and SpecificityUterine NeoplasmsConceptsSingle-agent chemotherapyLow HER-2/neu expressionCell linesHER-2/neu expressionEffective chemotherapy regimensPlatinum-based chemotherapySerous papillary adenocarcinomaHalf-maximum inhibitory concentrationPlatinum compoundsLow half-maximum inhibitory concentrationChemotherapy regimensAdverse prognosisPapillary adenocarcinomaCarcinoma cell linesNeu expressionNeu overexpressionChemotherapy agentsPapillary carcinoma cell line
2004
Current treatment options for endometrial cancer
Santin AD, Bellone S, O’Brien T, Pecorelli S, Cannon MJ, Roman JJ. Current treatment options for endometrial cancer. Expert Review Of Anticancer Therapy 2004, 4: 679-689. PMID: 15270671, DOI: 10.1586/14737140.4.4.679.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCell DifferentiationCisplatinDoxorubicinEndometrial NeoplasmsFemaleHumansHysterectomyNeoplasm InvasivenessNeoplasm Recurrence, LocalOvariectomyPaclitaxelPrognosisRadiotherapy, AdjuvantReceptor, ErbB-2Risk FactorsSurvival AnalysisTrastuzumabConceptsEndometrial cancerMyometrial invasionStage I endometrial cancer patientsLow-toxicity regimenEndometrial cancer patientsLymph node dissectionRecurrent endometrial cancerTotal abdominal hysterectomyClear cell histologyCornerstone of treatmentPostoperative radiation therapyImportant prognostic factorCurrent treatment optionsCombination of cisplatinFemale genital tractAttractive therapeutic strategyMajority of casesType II receptorExtrapelvic recurrenceAbdominal hysterectomyNode dissectionPelvic radiotherapyPelvic recurrenceSystemic chemotherapyVaginal bleeding