2019
Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial
Konstantinopoulos PA, Barry WT, Birrer M, Westin SN, Cadoo KA, Shapiro GI, Mayer EL, O'Cearbhaill RE, Coleman RL, Kochupurakkal B, Whalen C, Curtis J, Farooq S, Luo W, Eismann J, Buss MK, Aghajanian C, Mills GB, Palakurthi S, Kirschmeier P, Liu J, Cantley LC, Kaufmann SH, Swisher EM, D'Andrea AD, Winer E, Wulf GM, Matulonis UA. Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial. The Lancet Oncology 2019, 20: 570-580. PMID: 30880072, PMCID: PMC7025391, DOI: 10.1016/s1470-2045(18)30905-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Ovarian EpithelialDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFemaleGenome, HumanHumansMaximum Tolerated DoseMiddle AgedMutationOvarian NeoplasmsPhosphoinositide-3 Kinase InhibitorsPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsThiazolesTreatment OutcomeConceptsEpithelial ovarian cancerPhase 2 dosePI3K inhibitor alpelisibPrimary peritoneal cancerPhase 1b trialRecurrent breast cancerGermline BRCA mutationsOvarian cancerBreast cancerDose levelsPeritoneal cancerBRCA mutationsFallopian tubeCommon treatment-related grade 3High-grade serous histologyTreatment-related grade 3Breast Cancer Research FoundationDecreased neutrophil countDose-escalation cohortsDose-expansion cohortsTreatment-related deathsTriple negative histologyResponse Evaluation CriteriaSolid Tumors 1.1Key eligibility criteria
2013
A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer
Liu JF, Tolaney SM, Birrer M, Fleming GF, Buss MK, Dahlberg SE, Lee H, Whalen C, Tyburski K, Winer E, Ivy P, Matulonis UA. A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. European Journal Of Cancer 2013, 49: 2972-2978. PMID: 23810467, PMCID: PMC3956307, DOI: 10.1016/j.ejca.2013.05.020.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCapsulesCarcinoma, Ovarian EpithelialDiarrheaDose-Response Relationship, DrugDrug Administration ScheduleFatigueFemaleHumansMiddle AgedNauseaNeoplasm Recurrence, LocalNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneReceptors, Vascular Endothelial Growth FactorTabletsTreatment OutcomeConceptsTriple-negative breast cancerOvarian cancer patientsOverall response rateCombination of cediranibCancer patientsBreast cancerDose levelsMetastatic triple-negative breast cancerEvaluable breast cancer patientsPARP inhibitorsClinical benefit rateGrade 3 fatigueGrade 3 hypertensionPhase 2 dosingVascular endothelial growth factor receptorResponse Evaluation CriteriaSolid Tumors 1.1Endothelial growth factor receptorPhase 1 trialBreast cancer patientsDose-escalation designHighest dose levelPolymerase inhibitor olaparibCA125 criteriaGrowth factor receptor
2008
Dose-escalation of filgrastim does not improve efficacy: Clinical tolerability and long-term follow-up on CALGB study 9141 adjuvant chemotherapy for node-positive breast cancer patients using dose-intensified doxorubicin plus cyclophosphamide followed by paclitaxel
Liu MC, Demetri GD, Berry DA, Norton L, Broadwater G, Robert NJ, Duggan D, Hayes DF, Henderson IC, Lyss A, Hopkins J, Kaufman PA, Marcom PK, Younger J, Lin N, Tkaczuk K, Winer EP, Hudis CA, B F. Dose-escalation of filgrastim does not improve efficacy: Clinical tolerability and long-term follow-up on CALGB study 9141 adjuvant chemotherapy for node-positive breast cancer patients using dose-intensified doxorubicin plus cyclophosphamide followed by paclitaxel. Cancer Treatment Reviews 2008, 34: 223-230. PMID: 18234424, PMCID: PMC2651678, DOI: 10.1016/j.ctrv.2007.11.004.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDisease-Free SurvivalDoxorubicinFemaleFilgrastimFollow-Up StudiesGranulocyte Colony-Stimulating FactorHumansLymphatic MetastasisMiddle AgedPaclitaxelPilot ProjectsRecombinant ProteinsConceptsG-CSF supportGrowth factor supportRelapse-free survivalClinical outcomesDose levelsG-CSFFactor supportConventional doseClinical trialsBreast cancerNode-positive invasive breast cancerNode-positive breast cancer patientsAcute treatment-related toxicityHematopoietic growth factor supportOperable primary breast cancerAdjuvant chemotherapy regimenDose-intensified regimenDose-intensive regimensEarly study withdrawalNode-positive patientsTreatment-related toxicityHormone receptor statusInvasive breast cancerOverall survival ratePrimary breast cancer
2006
Phase I pharmacokinetic (PK), and pharmacodynamic (PD) trial of the novel oral Notch inhibitor MK-0752 in patients (pts) with advanced breast cancer (BC) and other solid tumors
Krop I, Kosh M, Fearen I, Savoie J, Dallob A, Matthews C, Stone J, Winer E, Freedman S, Lorusso P. Phase I pharmacokinetic (PK), and pharmacodynamic (PD) trial of the novel oral Notch inhibitor MK-0752 in patients (pts) with advanced breast cancer (BC) and other solid tumors. Journal Of Clinical Oncology 2006, 24: 10574-10574. DOI: 10.1200/jco.2006.24.18_suppl.10574.Peer-Reviewed Original ResearchGrade 3 diarrheaAdvanced breast cancerBreast cancerPlasma AbetaDay 1Notch intracellular domainDose levelsSolid tumorsAccelerated dose escalationGamma-SecretaseGrade 2/3 fatigueMean PK parametersSubset of ptsElevated liver transaminasesAdvanced solid tumorsDaily oral dosingIntermittent dosing scheduleAnalysis of efficacyHuman breast cancerBC cell proliferationInhibition of NotchAbdominal crampingLiver transaminasesDosing schedulesPharmacodynamic trial
2003
Phase II, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer.
Buzdar A, O’Shaughnessy J, Booser DJ, Pippen JE, Jones SE, Munster PN, Peterson P, Melemed AS, Winer E, Hudis C. Phase II, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer. Journal Of Clinical Oncology 2003, 21: 1007-14. PMID: 12637464, DOI: 10.1200/jco.2003.06.108.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalBiomarkers, TumorBreast NeoplasmsDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleDrug Resistance, NeoplasmEndometriumEstrogen Receptor ModulatorsFemaleHumansMiddle AgedPatient SelectionPiperidinesReceptors, EstrogenSurvival AnalysisTamoxifenThiophenesTreatment OutcomeConceptsMetastatic breast cancerClinical benefit rateBreast cancerTamoxifen refractoryTR patientsResponse rateDose levelsEnd pointSelective estrogen receptor modulatorsPhase II studyPrimary end pointSecondary end pointsTumor response rateDouble-blind studyEstrogen receptor statusMetastatic disease sitesEstrogen receptor modulatorsTreatment of TSSimilar TTPTamoxifen therapyII studyDaily doseLonger TTPReceptor statusDose-dependent toxicity
2001
Phase II Evaluation Of Thalidomide In Patients With Metastatic Breast Cancer
Baidas S, Winer E, Fleming G, Harris L, Pluda J, Crawford J, Yamauchi H, Isaacs C, Hanfelt J, Tefft M, Flockhart D, Johnson, Hawkins M, Lippman M, Hayes D. Phase II Evaluation Of Thalidomide In Patients With Metastatic Breast Cancer. Journal Of The Peripheral Nervous System 2001, 6: 65-66. DOI: 10.1046/j.1529-8027.2001.01008-20.x.Peer-Reviewed Original ResearchMetastatic breast cancerWeeks of treatmentProgressive diseaseBreast cancerDose levelsProgressive metastatic breast cancerGrowth factor serum levelsSingle-agent thalidomideFactor serum levelsPhase II evaluationLack of efficacyDifferent patient populationsLow dose levelsAngiogenic growth factorsStable diseaseDry mouthAdverse eventsSkin rashComplete responseSerum levelsPatient populationWeek 16II evaluationGrade 3Patients
2000
Phase II evaluation of thalidomide in patients with metastatic breast cancer.
Baidas S, Winer E, Fleming G, Harris L, Pluda J, Crawford J, Yamauchi H, Isaacs C, Hanfelt J, Tefft M, Flockhart D, Johnson M, Hawkins M, Lippman M, Hayes D. Phase II evaluation of thalidomide in patients with metastatic breast cancer. Journal Of Clinical Oncology 2000, 18: 2710-7. PMID: 10894870, DOI: 10.1200/jco.2000.18.14.2710.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsBreast NeoplasmsDrug Administration ScheduleEndothelial Growth FactorsFemaleFibroblast Growth Factor 2Growth SubstancesHumansLymphokinesMatrix MetalloproteinasesMiddle AgedNeoplasm MetastasisProspective StudiesThalidomideTumor Necrosis Factor-alphaVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsMetastatic breast cancerWeeks of treatmentProgressive diseaseBreast cancerDose levelsProgressive metastatic breast cancerGrowth factor serum levelsSingle-agent thalidomideFactor serum levelsPhase II evaluationLack of efficacyDifferent patient populationsLow dose levelsAngiogenic growth factorsStable diseaseDry mouthAdverse eventsSkin rashComplete responseSerum levelsPatient populationWeek 16II evaluationGrade 3Patients