2013
A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer
Lin NU, Seah DS, Gelman R, Desantis S, Mayer EL, Isakoff S, DiPiro P, Krop IE, Come SE, Weckstein D, Winer EP, Burstein HJ. A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Research And Treatment 2013, 139: 403-410. PMID: 23645007, DOI: 10.1007/s10549-013-2551-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerGrade 3/4 non-hematologic toxicitiesHER2-positive metastatic breast cancerNon-hematologic toxicitiesTreatment-related toxicityBreast cancerCommon treatment-related toxicitiesFirst-line patientsProtocol-based therapySecond-line cohortSecond-line patientsSecond-line settingPhase II studyProportion of patientsCombination of vinorelbineCo-primary endpointsEligible patientsFebrile neutropeniaMedian PFSII studyMedian durationObjective responsePrior linesUnacceptable toxicityMedian age
2009
International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy
Cardoso F, Bedard PL, Winer EP, Pagani O, Senkus-Konefka E, Fallowfield LJ, Kyriakides S, Costa A, Cufer T, Albain KS, Force O. International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy. Journal Of The National Cancer Institute 2009, 101: 1174-1181. PMID: 19657108, PMCID: PMC2736293, DOI: 10.1093/jnci/djp235.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnthracyclinesAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCapecitabineComorbidityCongresses as TopicCross-Over StudiesDeoxycytidineDrug Administration ScheduleEuropeEvidence-Based MedicineFemaleFluorouracilHumansInternational CooperationKarnofsky Performance StatusMenopausePatient SelectionPractice Guidelines as TopicQuality of LifeRandomized Controlled Trials as TopicSeverity of Illness IndexSocioeconomic FactorsTaxoidsVinblastineVinorelbineConceptsMetastatic breast cancerSequential single-agent chemotherapySingle-agent chemotherapyBreast cancerEarly-stage breast cancerEuropean Breast Cancer ConferenceSequential single agentsPatient-rated qualityRapid clinical progressionDisease-related factorsImpact of therapySequential monotherapyAdvanced diseaseSequential therapyVisceral metastasesCytotoxic chemotherapyTask ForceClinical progressionPredictive factorsTreatment optionsCancer ConferenceRapid symptomsSingle agentChemotherapyInternational guidelines
2008
VEGF as a Marker for Outcome Among Advanced Breast Cancer Patients Receiving anti-VEGF Therapy with Bevacizumab and Vinorelbine Chemotherapy
Burstein HJ, Chen YH, Parker LM, Savoie J, Younger J, Kuter I, Ryan PD, Garber JE, Chen H, Campos SM, Shulman LN, Harris LN, Gelman R, Winer EP. VEGF as a Marker for Outcome Among Advanced Breast Cancer Patients Receiving anti-VEGF Therapy with Bevacizumab and Vinorelbine Chemotherapy. Clinical Cancer Research 2008, 14: 7871-7877. PMID: 19047116, DOI: 10.1158/1078-0432.ccr-08-0593.Peer-Reviewed Original ResearchConceptsAdvanced breast cancer patientsRefractory breast cancerBreast cancer patientsBreast cancerPlasma VEGFCancer patientsTreatment outcomesSide effectsAnti-vascular endothelial growth factor therapyAdequate end-organ functionEndothelial growth factor therapyImportant new treatment modalityTumor hormone receptor statusMonoclonal anti-VEGF antibodyPrior chemotherapy regimensEnd-organ functionHormone receptor statusAnti-VEGF therapyMetastatic breast cancerGrowth factor therapyNew treatment modalitiesWarrants further evaluationAnti-VEGF antibodyBaseline VEGFEligible patients
2007
Trastuzumab plus vinorelbine or taxane chemotherapy for HER2‐overexpressing metastatic breast cancer: The trastuzumab and vinorelbine or taxane study
Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert‐Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2‐overexpressing metastatic breast cancer: The trastuzumab and vinorelbine or taxane study. Cancer 2007, 110: 965-972. PMID: 17614302, DOI: 10.1002/cncr.22885.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlopeciaAnemiaAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsConstipationDisease ProgressionDrug Administration ScheduleFatigueFemaleHumansKaplan-Meier EstimateMiddle AgedNauseaNeoplasm MetastasisPaclitaxelProspective StudiesReceptor, ErbB-2TrastuzumabTreatment OutcomeVinblastineVinorelbineConceptsMetastatic breast cancerBreast cancerTrastuzumab armEpisodes of cardiotoxicityFirst-line therapyDermatologic toxicitiesEvaluable patientsPrior chemotherapyVinorelbine therapyAdvanced diseaseChemotherapy regimenEligible patientsGastrointestinal toxicityPoor accrualTaxane chemotherapyTaxane therapyMore anemiaMedian timeTrastuzumab treatmentFluid retentionDisease progressionChemotherapy agentsTreatment decisionsVinorelbineSide effectsPredictors of Resistance to Preoperative Trastuzumab and Vinorelbine for HER2-Positive Early Breast Cancer
Harris LN, You F, Schnitt SJ, Witkiewicz A, Lu X, Sgroi D, Ryan PD, Come SE, Burstein HJ, Lesnikoski BA, Kamma M, Friedman PN, Gelman R, Iglehart JD, Winer EP. Predictors of Resistance to Preoperative Trastuzumab and Vinorelbine for HER2-Positive Early Breast Cancer. Clinical Cancer Research 2007, 13: 1198-1207. PMID: 17317830, DOI: 10.1158/1078-0432.ccr-06-1304.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDoxorubicinDrug Resistance, NeoplasmFemaleGenes, erbB-2HumansMalePredictive Value of TestsPreoperative CareReceptor, ErbB-2TrastuzumabVinblastineVinorelbineConceptsPathologic complete responsePreoperative trastuzumabBreast cancerClinical responseComplete responseStage II/III breast cancerHER2-positive early breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Clinical complete responseEarly breast cancerGrowth factor receptor 2Estrogen receptor statusPositive breast cancerPredictors of responseBasal-like phenotypeInsulin-like growthFactor receptor 2Predictors of resistanceReceptor membrane expressionExtremes of responseGrowth factor pathwaysLow response rateGrowth factor receptorPreoperative treatment
2005
Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy
Burstein HJ, Lieberman G, Slamon DJ, Winer EP, Klein P. Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy. Annals Of Oncology 2005, 16: 1772-1777. PMID: 16150805, DOI: 10.1093/annonc/mdi371.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCentral Nervous System NeoplasmsCyclophosphamideDisease ProgressionDoxorubicinFemaleFollow-Up StudiesGene AmplificationHumansIn Situ Hybridization, FluorescencePaclitaxelPrevalenceReceptor, ErbB-2Survival RateTime FactorsTrastuzumabVinblastineVinorelbineConceptsTrastuzumab-based therapyMetastatic breast cancerHER2-overexpressing metastatic breast cancerCentral nervous system metastasesNervous system metastasesBreast cancerCNS progressionCNS metastasesFirst-line trastuzumab-based therapyHER2-positive metastatic breast cancerMulticenter phase II trialAdvanced breast cancerFirst-line treatmentPhase II trialPhase III studyTrastuzumab-based treatmentPrimary breast cancerHER2 gene amplificationGene amplificationMeasurable diseaseCNS recurrenceII trialIII studyMetastatic diseasePatient survival
2003
Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm.
Burstein HJ, Harris LN, Marcom PK, Lambert-Falls R, Havlin K, Overmoyer B, Friedlander RJ, Gargiulo J, Strenger R, Vogel CL, Ryan PD, Ellis MJ, Nunes RA, Bunnell CA, Campos SM, Hallor M, Gelman R, Winer EP. Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm. Journal Of Clinical Oncology 2003, 21: 2889-95. PMID: 12885806, DOI: 10.1200/jco.2003.02.018.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlgorithmsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDisease ProgressionFemaleHeart DiseasesHumansInfusions, IntravenousMiddle AgedPredictive Value of TestsReceptor, ErbB-2ROC CurveSurvival AnalysisTrastuzumabTreatment OutcomeVinblastineVinorelbineConceptsLeft ventricular ejection fractionMetastatic breast cancerHER2-positive metastatic breast cancerBreast cancerHER2 extracellular domainResponse rateEjection fractionTumor markersNormal left ventricular ejection fractionMulticenter phase II studyMulticenter phase II trialPositive advanced breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Prior adjuvant chemotherapySafety of trastuzumabFirst-line chemotherapyPhase II studySymptomatic heart failureAdvanced breast cancerBaseline ejection fractionFirst-line therapyFirst-line treatmentPhase II trialTrastuzumab-based therapy
2002
Trastuzumab/chemotherapy combinations in metastatic breast cancer.
Ligibel JA, Winer EP. Trastuzumab/chemotherapy combinations in metastatic breast cancer. Seminars In Oncology 2002, 29: 38-43. PMID: 12138396, DOI: 10.1053/sonc.2002.34054.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerHER2-overexpressing metastatic breast cancerUse of trastuzumabBreast cancerRandomized phase III clinical trialsHER2-overexpressing breast cancerPhase III clinical trialsHER2/neu proteinAdvanced breast cancerFirst-line treatmentForm of chemotherapyHumanized monoclonal antibodyLonger survival durationHigh response rateNew chemotherapy drugsAdjuvant settingChemotherapy combinationsSurvival durationClinical trialsFurther trialsEfficacious treatmentPlatinum agentsSingle agentUS FoodDrug Administration
2001
New Combinations with Herceptin® in Metastatic Breast Cancer
Winer E, Burstein H. New Combinations with Herceptin® in Metastatic Breast Cancer. Oncology 2001, 61: 50-57. PMID: 11694788, DOI: 10.1159/000055402.Peer-Reviewed Original ResearchMeSH KeywordsAnastrozoleAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicCyclophosphamideDeoxycytidineDoxorubicinDrug InteractionsDrug SynergismEpirubicinFemaleFluorouracilGemcitabineHeart DiseasesHematologic DiseasesHumansMethotrexateNeoplasm MetastasisNitrilesOrganoplatinum CompoundsPaclitaxelTamoxifenThiotepaTrastuzumabTreatment OutcomeTriazolesVinblastineVinorelbineConceptsMetastatic breast cancerBreast cancerHormonal agentsSide effectsHER2-positive metastatic breast cancerPivotal phase III trialsHER2-positive breast cancerSingle-agent vinorelbineCombination of trastuzumabPhase II trialPhase III trialsMajor side effectsPossible side effectsHormonal therapyII trialIII trialsCombination regimensPreclinical dataClinical trialsMost womenBetter outcomesTrastuzumabCancerTrialsLiposomal formulationNew cytotoxic agents and schedules for advanced breast cancer
Burstein H, Bunnell C, Winer E. New cytotoxic agents and schedules for advanced breast cancer. Seminars In Oncology 2001, 28: 344-358. DOI: 10.1053/sonc.2001.26146.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCisplatinClinical Trials as TopicDeoxycytidineDocetaxelDoxorubicinEnzyme InhibitorsFemaleFluorouracilGemcitabineHumansLiposomesPaclitaxelTaxoidsTopoisomerase I InhibitorsTrastuzumabVinblastineVinorelbineConceptsAdvanced breast cancerBreast cancerSide effectsUse of chemotherapyCombination of chemotherapyNovel biological agentsNew cytotoxic agentsTreatment of womenSuch biological therapiesCytotoxic chemotherapyBiological therapyVariety of agentsClinical activityAvailable agentsBetter survivalChemotherapyOral chemotherapeuticsCancerCytotoxic agentsWomenBiological agentsAgentsTherapyImportant studiesNew cytotoxic agents and schedules for advanced breast cancer
Burstein H, Bunnell C, Winer E. New cytotoxic agents and schedules for advanced breast cancer. Seminars In Oncology 2001, 28: 344-358. PMID: 11498829, DOI: 10.1016/s0093-7754(01)90129-0.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCisplatinClinical Trials as TopicDeoxycytidineDocetaxelDoxorubicinEnzyme InhibitorsFemaleFluorouracilGemcitabineHumansLiposomesPaclitaxelTaxoidsTopoisomerase I InhibitorsTrastuzumabVinblastineVinorelbineConceptsAdvanced breast cancerBreast cancerSide effectsUse of chemotherapyCombination of chemotherapyNovel biological agentsNew cytotoxic agentsTreatment of womenSuch biological therapiesCytotoxic chemotherapyBiological therapyVariety of agentsClinical activityAvailable agentsBetter survivalChemotherapyOral chemotherapeuticsCancerCytotoxic agentsWomenBiological agentsAgentsTherapyImportant studiesClinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer.
Burstein H, Kuter I, Campos S, Gelman R, Tribou L, Parker L, Manola J, Younger J, Matulonis U, Bunnell C, Partridge A, Richardson P, Clarke K, Shulman L, Winer E. Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer. Journal Of Clinical Oncology 2001, 19: 2722-30. PMID: 11352965, DOI: 10.1200/jco.2001.19.10.2722.Peer-Reviewed Original ResearchConceptsGrade 2 cardiac toxicityAdvanced breast cancerBreast cancerResponse rateCardiac toxicityHER2-overexpressing metastatic breast cancerOnly grade 4 toxicityHER2-positive breast cancerCumulative doxorubicin doseGrade 4 toxicityStudy of trastuzumabSymptomatic heart failureThird-line therapyFirst-line therapyType of chemotherapyMetastatic breast cancerPercent of womenHigh response rateConcurrent trastuzumabPrior chemotherapyWeekly vinorelbineMetastatic diseasePositive patientsHeart failureDoxorubicin dose
1999
Phase I study of Doxil and vinorelbine in metastatic breast cancer
Burstein HJ, Ramirez MJ, Petros WP, Clarke KD, Warmuth MA, Marcom PK, Matulonis UA, Parker LM, Harris LN, Winer EP. Phase I study of Doxil and vinorelbine in metastatic breast cancer. Annals Of Oncology 1999, 10: 1113-1116. PMID: 10572612, DOI: 10.1023/a:1008323200102.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerM2 days 1Breast cancerDay 1Grade 2 cardiac toxicityPrior anthracycline-based chemotherapyAnthracycline-based chemotherapyPhase II studyFirst treatment cyclePhase I studiesDose escalation schemeFavorable toxicity profilePharmacokinetic studyActive chemotherapeutic agentsHigher doxorubicin concentrationsDoxil administrationVinorelbine administrationSignificant nauseaII studySevere neutropeniaCombination chemotherapyCardiac toxicityCombination therapyEscalation schemeI studiesVinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older
Vogel C, O’Rourke M, Winer E, Hochster H, Chang A, Adamkiewicz B, White R, McGuirt C. Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older. Annals Of Oncology 1999, 10: 397-402. PMID: 10370781, DOI: 10.1023/a:1008364222793.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAgingAntineoplastic Agents, PhytogenicBreast NeoplasmsDisease-Free SurvivalDose-Response Relationship, DrugDrug Administration ScheduleFemaleFollow-Up StudiesHumansInfusions, IntravenousMiddle AgedProspective StudiesSeverity of Illness IndexTreatment OutcomeVinblastineVinorelbineConceptsAdvanced breast cancerDose-limiting toxicityBreast cancerSide effectsNonhematologic toxicityElderly patientsMeasurable advanced breast cancerMajor dose-limiting toxicityActivity of vinorelbineMedian dose intensityFirst-line chemotherapyObjective response rateFirst-line therapyPhase II trialSubjective side effectsInjection site reactionsWomen 60 yearsGastrointestinal side effectsGeneralized painIntravenous vinorelbinePrior chemotherapyAbdominal painChest painII trialCytotoxic chemotherapyInability to escalate vinorelbine dose intensity using a daily × 3 schedule with and without filgrastim in patients with metastatic breast cancer
Havlin K, Ramirez M, Legler C, Harris L, Matulonis U, Hohneker J, Hayes D, Winer E. Inability to escalate vinorelbine dose intensity using a daily × 3 schedule with and without filgrastim in patients with metastatic breast cancer. Cancer Chemotherapy And Pharmacology 1999, 43: 68-72. PMID: 9923543, DOI: 10.1007/s002800050864.Peer-Reviewed Original ResearchConceptsDana-Farber Cancer InstituteDuke University Medical CenterDose-limiting toxicityGrowth factor supportGrade III neurotoxicityMetastatic breast cancerFebrile neutropeniaBreast cancerFactor supportNonhematologic toxicityStarting doseDose intensityDay 4Stage IV breast cancerMajor dose-limiting toxicityAddition of filgrastimAlternative treatment regimenGrade III stomatitisGrade III vomitingGrade IV mucositisGrade IV thrombocytopeniaGreater nonhematologic toxicityPerformance status 0Prior chemotherapy regimensSemisynthetic vinca alkaloid
1995
Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer.
Jones S, Winer E, Vogel C, Laufman L, Hutchins L, O'Rourke M, Lembersky B, Budman D, Bigley J, Hohneker J. Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer. Journal Of Clinical Oncology 1995, 13: 2567-74. PMID: 7595708, DOI: 10.1200/jco.1995.13.10.2567.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibiotics, AntineoplasticAntineoplastic AgentsBreast NeoplasmsDisease ProgressionDrug Administration ScheduleDrug Resistance, NeoplasmFemaleHematologic DiseasesHumansInjections, IntravenousMelphalanMiddle AgedProportional Hazards ModelsProspective StudiesQuality of LifeSurvival RateVinblastineVinorelbineConceptsQuality of lifeAdvanced breast cancerCancer-related symptomsTreatment failureBreast cancerALK patientsSurvival rateStabilization of diseaseEfficacy end pointTumor response ratePopulation of patientsMedian survival rateCommon toxicitiesProspective multicenterObjective responseSeptic deathSurvival benefitRandomized comparisonPatient populationPatientsIntergroup differencesTreatment centersResponse rateEnd pointVinorelbine tartrateOral vinorelbine (Navelbine) in the treatment of advanced breast cancer.
Winer EP, Chu L, Spicer DV. Oral vinorelbine (Navelbine) in the treatment of advanced breast cancer. Seminars In Oncology 1995, 22: 72-8; discussion 78-9. PMID: 7740337.Peer-Reviewed Original ResearchConceptsAdvanced breast cancerOral vinorelbineBreast cancerIntravenous administrationResponse rateMulticenter phase II trialAdvanced breast cancer patientsPhase II trialHigh first-pass effectBreast cancer patientsFirst-pass effectPharmacokinetics of vinorelbineII trialCancer patientsClinical investigationVinorelbineHigh clearance rateSoft gelatin capsulesClearance ratePatientsCancerPharmacokinetic studyLow bioavailabilityAdministrationGelatin capsules
1994
Pharmacokinetic, bioavailability, and feasibility study of oral vinorelbine in patients with solid tumors.
Rowinsky EK, Noe DA, Trump DL, Winer EP, Lucas VS, Wargin WA, Hohneker JA, Lubejko B, Sartorius SE, Ettinger DS. Pharmacokinetic, bioavailability, and feasibility study of oral vinorelbine in patients with solid tumors. Journal Of Clinical Oncology 1994, 12: 1754-63. PMID: 8083697, DOI: 10.1200/jco.1994.12.9.1754.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseOral administrationOral formulationOral vinorelbineGrade 3Large first-pass effectLower starting doseSemisynthetic vinca alkaloidChronic oral administrationHepatic blood flowPhase II evaluationPharmacokinetic studyDivided-dose scheduleMaximum plasma concentrationFirst-pass effectSteady-state volumeGelatin capsulesPlasma drug dispositionPharmacologic exposuresPrincipal toxicityStarting doseDose escalationOral dosesOral doseCancer patients