2023
Platinum Sensitivity in IDH1/2 Mutated Intrahepatic Cholangiocarcinoma: Not All “BRCAness” Is Created Equal
Doroshow D, Wei W, Mehrotra M, Sia D, Eder J, Bindra R, Houldsworth J, LoRusso P, Walther Z. Platinum Sensitivity in IDH1/2 Mutated Intrahepatic Cholangiocarcinoma: Not All “BRCAness” Is Created Equal. Cancer Investigation 2023, 41: 646-655. PMID: 37505929, DOI: 10.1080/07357907.2023.2242957.Peer-Reviewed Original ResearchConceptsClinical benefit rateIntrahepatic cholangiocarcinomaPlatinum sensitivityUnresectable intrahepatic cholangiocarcinomaObjective response rateMulticenter retrospective studyHomologous recombination repairDefective homologous recombination (HR) repairPrimary endpointPlatinum chemotherapyRetrospective studyPreclinical dataBenefit rateWildtype tumorsResponse rateMT tumorsWT diseasePatientsGene defectsCholangiocarcinomaTumors
2017
A Phase I/Ib Study of Enzalutamide Alone and in Combination with Endocrine Therapies in Women with Advanced Breast Cancer
Schwartzberg LS, Yardley D, Elias A, Patel M, LoRusso P, Burris HA, Gucalp A, Peterson A, Blaney M, Steinberg J, Gibbons J, Traina TA. A Phase I/Ib Study of Enzalutamide Alone and in Combination with Endocrine Therapies in Women with Advanced Breast Cancer. Clinical Cancer Research 2017, 23: 4046-4054. PMID: 28280092, DOI: 10.1158/1078-0432.ccr-16-2339.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnastrozoleAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsAromatase InhibitorsBenzamidesBreast NeoplasmsCytochrome P-450 CYP3ADose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFemaleHumansMiddle AgedNeoplasm StagingNitrilesPhenylthiohydantoinPostmenopauseReceptors, EstrogenReceptors, ProgesteroneTriazolesConceptsEndocrine therapyEnzalutamide monotherapyBreast cancerEstrogen receptor-positive/progesterone receptor-positive breast cancerProgesterone receptor-positive breast cancerCytochrome P450 3A4 inducerRandomized phase II studyReceptor-positive breast cancerDose-expansion cohortsEffect of enzalutamidePhase II studyAdvanced breast cancerAndrogen receptor signalingBreast cancer modelClin Cancer ResDose modificationII studyPharmacokinetic interactionsPreclinical dataProstate cancerIb studyAdditional cohortMonotherapyCancer modelExemestanePhase I study combining the aurora kinase A (AURKA) inhibitor alisertib (Ali) with mFOLFOX in gastrointestinal (GI) cancer.
Goff L, Azad N, Stein S, Whisenant J, Vaishampayan U, Hochster H, Connolly R, Weise A, LoRusso P, El-Rifai W, Berlin J. Phase I study combining the aurora kinase A (AURKA) inhibitor alisertib (Ali) with mFOLFOX in gastrointestinal (GI) cancer. Journal Of Clinical Oncology 2017, 35: 2593-2593. DOI: 10.1200/jco.2017.35.15_suppl.2593.Peer-Reviewed Original ResearchGI cancersStandard platinum-based therapyCorrelative biomarker studyDisease control rateMost frequent toxicitiesPreliminary clinical activityPlatinum-based therapyMajority of ptsEvaluable ptsStable diseaseEligible patientsFrequent toxicitiesHematologic toxicityPartial responseStandard therapyDose escalationInhibition of AURKAControl rateGastrointestinal cancerPreclinical dataClinical activityPlatinum agentsDose levelsInhibitor alisertibOptimal timing window
2013
Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic adrenocortical carcinoma
Naing A, LoRusso P, Fu S, Hong D, Chen H, Doyle L, Phan A, Habra M, Kurzrock R. Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic adrenocortical carcinoma. British Journal Of Cancer 2013, 108: 826-830. PMID: 23412108, PMCID: PMC3590681, DOI: 10.1038/bjc.2013.46.Peer-Reviewed Original ResearchConceptsIGF-1R inhibitorsAdrenocortical carcinomaStable diseaseAggressive endocrine malignancyHuman IgG1 monoclonal antibodyProlonged stable diseaseMetastatic adrenocortical carcinomaGrowth factor receptor antibodyEffective systemic chemotherapyMTOR inhibitor temsirolimusIGF-1 receptorIgG1 monoclonal antibodyFrequent toxicitiesPrior therapySystemic chemotherapyMedian ageReceptor antibodiesPreclinical dataEndocrine malignancyMedian numberIGF-1RPatientsTemsirolimusCixutumumabGrade 1
2012
Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.
Modi S, Elias A, LoRusso P, Samant M, Guardino E, Althaus B, Krop I. Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab. Journal Of Clinical Oncology 2012, 30: 528-528. DOI: 10.1200/jco.2012.30.15_suppl.528.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerMetastatic breast cancerT-DM1Prior systemic therapyPhase Ib studyPhase II studyDose-escalation studySingle-agent activityDuration of responseDose escalation schemeFuture clinical trialsDLT criteriaII studyMedian ageSystemic therapyExtension trialPreclinical dataTrastuzumab emtansineClinical trialsMedian numberToxicity CriteriaBreast cancerIb studyPhase IbQ3wActivity of insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic refractory adrenocortical carcinoma.
Naing A, LoRusso P, Fu S, Hong D, Chen H, Doyle L, Phan A, Habra M, Kurzrock R. Activity of insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic refractory adrenocortical carcinoma. Journal Of Clinical Oncology 2012, 30: 4639-4639. DOI: 10.1200/jco.2012.30.15_suppl.4639.Peer-Reviewed Original ResearchIGF-1R inhibitorsAdrenocortical carcinomaStable diseaseHuman IgG1 monoclonal antibodyProlonged stable diseaseGrowth factor receptor antibodyEffective systemic chemotherapyGrowth factor 1 receptorInsulin growth factor-1 receptorMTOR inhibitor temsirolimusFactor 1 receptorIgG1 monoclonal antibodyPrior therapyFrequent toxicitiesSystemic chemotherapyMedian agePreclinical dataMedian numberTemsirolimusPatientsCixutumumabMTOR pathwayGrade 1Monoclonal antibodiesCarcinoma
2007
A phase 1 dynamic accelerated titration dose escalation study of the vascular disrupting agent NPI-2358
Spear M, LoRusso P, Tolcher A, Lin C, Wang D, Heath E, Lloyd G, Cropp G, Papadopoulos K. A phase 1 dynamic accelerated titration dose escalation study of the vascular disrupting agent NPI-2358. Journal Of Clinical Oncology 2007, 25: 14097-14097. DOI: 10.1200/jco.2007.25.18_suppl.14097.Peer-Reviewed Original ResearchStable diseaseAdverse eventsDrug accumulationGrade 2 adverse eventsMultiple murine tumor modelsDose-escalation studyDose-limiting toxicityObserved adverse eventsPhase 1 studyTumor vascular endothelial cellsDirect cytotoxic activityMurine tumor modelsVascular endothelial cellsTumor vascular collapseEscalation studyFirst doseDose escalationSafety profileEfficacious dosePreclinical dataTumor regressionPancreatic adenocarcinomaAverage CmaxVascular collapsePK data