2024
Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors
Choi Y, Dharia N, Jun T, Chang J, Royer-Joo S, Yau K, Assaf Z, Aimi J, Sivakumar S, Montesion M, Sacher A, LoRusso P, Desai J, Schutzman J, Shi Z, group A. Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors. Clinical Cancer Research 2024, 30: of1-of10. PMID: 38995268, PMCID: PMC11369623, DOI: 10.1158/1078-0432.ccr-24-0255.Peer-Reviewed Original ResearchConceptsKRAS G12C mutationTumor fractionSolid tumorsTumor typesG12C mutationOn-treatment time pointsNon-small cell lung cancerMutational heterogeneityAssociated with tumor typeProgression-free survivalPlasma samplesPhase 1 studyCell lung cancerCycle 1 dayAssociated with patient outcomesVariant allele frequencyAssociated with responseCtDNA levelsCtDNA profilingMetastatic sitesTruncal mutationsTumor DNATreatment responseLung cancerTumor tissues
2023
A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors
Garralda E, Schram A, Bedard P, Schwartz G, Yuen E, McNeely S, Ribeiro S, Cunningham J, Wang Y, Urunuela A, Xu X, LoRusso P. A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors. The Oncologist 2023, 29: e131-e140. PMID: 37531083, PMCID: PMC10769797, DOI: 10.1093/oncolo/oyad215.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsAdvanced solid tumorsCyclin-dependent kinase 7Adverse eventsSolid tumorsPhase I dose-escalation studyI dose-escalation studyLimited clinical activityGastrointestinal adverse eventsDose-escalation studyDose-limiting toxicityPhase I trialBest overall responsePeak-trough fluctuationKinase 7Common toxicitiesStable diseaseAbdominal painPrimary endpointSecondary endpointsAdult patientsPartial responseComplete responseI trialMedian time
2020
Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti–c-Met Antibody, in Patients with Advanced Solid Tumors
Strickler JH, LoRusso P, Salgia R, Kang YK, Yen C, Lin CC, Ansell P, Motwani M, Wong S, Yue H, Wang L, Reilly E, Afar D, Naumovski L, Ramanathan RK. Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti–c-Met Antibody, in Patients with Advanced Solid Tumors. Molecular Cancer Therapeutics 2020, 19: 1210-1217. PMID: 32127466, DOI: 10.1158/1535-7163.mct-19-0529.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsSolid tumorsStable diseaseDose escalationCommon treatment-related adverse eventsAnti-c-Met antibodyTreatment-related adverse eventsDose-expansion phaseI Dose-EscalationAcceptable safety profileResponse Evaluation CriteriaDose-limiting toxicitySubset of patientsLinear pharmacokinetic profilePeak plasma concentrationAcute infusion reactionsHuman phase IDose cohortsDose expansionRECIST criteriaAdverse eventsEscalation cohortsInfusion reactionsObjective responsePartial responseDevelopment of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies
Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clinical Cancer Research 2020, 26: 1247-1257. PMID: 31527168, PMCID: PMC7528620, DOI: 10.1158/1078-0432.ccr-18-4071.Peer-Reviewed Original ResearchConceptsAdvanced malignanciesGrade treatment-related adverse eventsTreatment-related adverse eventsAdequate organ functionHigh interpatient variabilityFavorable PK profileOptimal dosing schemePrimary endpointAdverse eventsOral clearancePartial responseComplete responsePhase 1/2Terminal eliminationTolerability studyPatient populationPharmacodynamic profileInterpatient variabilityDosing schemesDistinct pharmacokineticsTherapeutic indexOrgan functionPK profilesExtraterminal (BET) inhibitorsTarget inhibitionA First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors
Varga A, Soria JC, Hollebecque A, LoRusso P, Bendell J, Huang SA, Wagle MC, Okrah K, Liu L, Murray E, Sanabria-Bohorquez SM, Tagen M, Dokainish H, Mueller L, Burris H. A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors. Clinical Cancer Research 2020, 26: 1229-1236. PMID: 31848189, DOI: 10.1158/1078-0432.ccr-19-2574.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedDose-Response Relationship, DrugFatigueFemaleHumansMaleMAP Kinase Signaling SystemMaximum Tolerated DoseMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NauseaNeoplasmsPatient SafetyProtein Kinase InhibitorsPyridonesPyrimidinesTissue DistributionVomitingConceptsBRAF-mutant colorectal cancerColorectal cancerAdverse eventsFDG-PETCommon drug-related adverse eventsSolid tumorsDrug-related adverse eventsPhase IPartial metabolic responseAcceptable safety profileAdvanced solid tumorsDose-proportional increaseGrade 3 rashMetastatic solid tumorsSerial tumor biopsiesSingle-agent activityBest overall responseHuman phase IMAPK pathway inhibitionMultiple tumor typesStable diseaseEscalation studyPartial responseOral inhibitorPharmacodynamic effects
2019
First-in-Human Study of Mivebresib (ABBV-075), an Oral Pan-Inhibitor of Bromodomain and Extra Terminal Proteins, in Patients with Relapsed/Refractory Solid Tumors
Piha-Paul SA, Sachdev JC, Barve M, LoRusso P, Szmulewitz R, Patel SP, Lara PN, Chen X, Hu B, Freise KJ, Modi D, Sood A, Hutti JE, Wolff J, O'Neil BH. First-in-Human Study of Mivebresib (ABBV-075), an Oral Pan-Inhibitor of Bromodomain and Extra Terminal Proteins, in Patients with Relapsed/Refractory Solid Tumors. Clinical Cancer Research 2019, 25: 6309-6319. PMID: 31420359, DOI: 10.1158/1078-0432.ccr-19-0578.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsDose escalationSolid tumorsStable diseaseSafety profileProstate cancerCommon grade 3/4 treatment-emergent adverse eventsGrade 3/4 treatment-emergent adverse eventsHuman studiesMost common treatment-emergent adverse eventsCommon treatment-emergent adverse eventsMedian progression-free survivalTolerable safety profilePhase II doseAdvanced solid tumorsProgression-free survivalRefractory solid tumorsPreliminary antitumor activityMalignant solid tumorsAminotransferase elevationEvaluable patientsDose expansionExpansion cohortGastrointestinal bleedAdverse eventsPhase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors
Jung KH, LoRusso P, Burris H, Gordon M, Bang YJ, Hellmann MD, Cervantes A, de Olza M, Marabelle A, Hodi FS, Ahn MJ, Emens LA, Barlesi F, Hamid O, Calvo E, McDermott D, Soliman H, Rhee I, Lin R, Pourmohamad T, Suchomel J, Tsuhako A, Morrissey K, Mahrus S, Morley R, Pirzkall A, Davis SL. Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors. Clinical Cancer Research 2019, 25: 3220-3228. PMID: 30770348, PMCID: PMC7980952, DOI: 10.1158/1078-0432.ccr-18-2740.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorHumansImidazolesIndoleamine-Pyrrole 2,3,-DioxygenaseIndolesMagnetic Resonance ImagingMiddle AgedNeoplasm MetastasisNeoplasm StagingNeoplasmsTomography, X-Ray ComputedTreatment OutcomeConceptsPD-L1 inhibitorsT cellsPartial responseAdvanced cancerDay 1Dose levelsCommon treatment-related AEsDose-escalation stageTreatment-related AEsAdvanced solid tumorsEffector T cellsRegulatory T cellsLinear pharmacokinetic profileLocal tumor microenvironmentInvestigational small-molecule inhibitorExpansion patientsKynurenine accumulationComplete responseImmune suppressionIntravenous infusionAcceptable safetyTryptophan depletionNavoximodAtezolizumabPlasma Kyn
2018
A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors
Ferrarotto R, Eckhardt G, Patnaik A, LoRusso P, Faoro L, Heymach J, Kapoun A, Xu L, Munster P. A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors. Annals Of Oncology 2018, 29: 1561-1568. PMID: 29726923, DOI: 10.1093/annonc/mdy171.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalCohort StudiesDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalNeoplasmsPrognosisReceptor, Notch1Salvage TherapySurvival RateTissue DistributionConceptsNotch1 pathway activationPartial responseSolid tumorsPathway activationAdverse eventsCommon drug-related adverse eventsDrug-related adverse eventsDose-expansion studyGrade 3 diarrheaGrade 3 fatigueUnconfirmed partial responseRefractory solid tumorsProlonged SDsDisease stabilizationExpansion cohortMain toxicityRECIST 1.1Dose escalationEfficacy signalsClinical benefitPharmacodynamic effectsPreliminary efficacyAssessable subjectsImmunohistochemistry assaysNonlinear pharmacokinetics
2017
A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors
Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmaña J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R. A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clinical Cancer Research 2017, 23: 4095-4106. PMID: 28264872, DOI: 10.1158/1078-0432.ccr-16-2796.Peer-Reviewed Original ResearchConceptsHigh-grade ovarian carcinomaObjective response rateInvestigator-assessed objective response rateOral rucaparibAdverse eventsCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsAspartate transaminase elevationsAsthenia/fatigueProtocol-defined criteriaRECIST version 1.1Phase II doseAdvanced solid tumorsProgression-free intervalSmall molecule PARP inhibitorsClin Cancer ResManageable toxicityPrior regimensPrimary endpointTransaminase elevationPlatinum therapyMultiple dosesOvarian carcinomaAlanine transaminaseClinical activityA 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 modelExemestane
2016
A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function
Li C, Agarwal P, Gibiansky E, Jin J, Dent S, Gonçalves A, Nijem I, Strasak A, Harle-Yge M, Chernyukhin N, LoRusso P, Girish S. A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function. Clinical Pharmacokinetics 2016, 56: 1069-1080. PMID: 27995530, DOI: 10.1007/s40262-016-0496-y.Peer-Reviewed Original ResearchConceptsNormal hepatic functionModerate hepatic impairmentHepatic impairmentMetastatic breast cancerHepatic functionTrastuzumab emtansineBreast cancerCycle 1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Phase I pharmacokinetic studyHuman epidermal growth factor receptorChild-Pugh criteriaMild hepatic impairmentT-DM1 3.6T-DM1 exposureGrowth factor receptor 2I pharmacokinetic studyFactor receptor 2Epidermal growth factor receptorGrowth factor receptorModerate cohortBaseline albuminT-DM1Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study
Nogova L, Sequist LV, Garcia J, Andre F, Delord JP, Hidalgo M, Schellens JH, Cassier PA, Camidge DR, Schuler M, Vaishampayan U, Burris H, Tian GG, Campone M, Wainberg ZA, Lim WT, LoRusso P, Shapiro GI, Parker K, Chen X, Choudhury S, Ringeisen F, Graus-Porta D, Porter D, Isaacs R, Buettner R, Wolf J. Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study. Journal Of Clinical Oncology 2016, 35: 157-165. PMID: 27870574, PMCID: PMC6865065, DOI: 10.1200/jco.2016.67.2048.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptorGrowth factor receptorUrothelial cancerSafety profileAntitumor activitySolid tumorsGenetic alterationsKinase inhibitorsDose-expansion studyFGFR genetic alterationsMethods Adult patientsMTD/RP2DCommon adverse eventsManageable safety profilePhase II doseSimilar safety profileAdvanced solid tumorsContinuous scheduleDose-limiting toxicityFactor receptorCell lung cancerGrowth factor receptor 1Tyrosine kinase inhibitorsFibroblast growth factor receptor 1Factor receptor 1Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity
Schwartz GK, Dickson MA, LoRusso P, Sausville EA, Maekawa Y, Watanabe Y, Kashima N, Nakashima D, Akinaga S. Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity. Cancer Science 2016, 107: 499-506. PMID: 26850678, PMCID: PMC4832855, DOI: 10.1111/cas.12906.Peer-Reviewed Original ResearchConceptsOral tyrosine kinase inhibitorTyrosine kinase inhibitorsIGF-1RSolid tumorsHuman Phase I StudyInsulin-like growth factor receptor 1Colon carcinoma xenograft modelKinase inhibitorsHuman epidermal growth factor receptorPhase I clinical trialDose of KWModest antitumor activityAdvanced solid tumorsMetastatic breast cancerPhase I studiesGrowth factor receptor 1Human IGF-1RHuman malignant cell linesEpidermal growth factor receptorFactor receptor 1Inhibitory activityEvaluable patientsGrowth factor receptorMalignant cell linesStable disease
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
Phase I study of humanized monoclonal antibody AVE1642 directed against the type 1 insulin-like growth factor receptor (IGF-1R), administered in combination with anticancer therapies to patients with advanced solid tumors
Macaulay V, Middleton M, Protheroe A, Tolcher A, Dieras V, Sessa C, Bahleda R, Blay J, LoRusso P, Mery-Mignard D, Soria J. Phase I study of humanized monoclonal antibody AVE1642 directed against the type 1 insulin-like growth factor receptor (IGF-1R), administered in combination with anticancer therapies to patients with advanced solid tumors. Annals Of Oncology 2012, 24: 784-791. PMID: 23104723, PMCID: PMC3574548, DOI: 10.1093/annonc/mds511.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsDeoxycytidineDiarrheaDocetaxelDoxorubicinErlotinib HydrochlorideFemaleGemcitabineHumansLeiomyosarcomaMaleMelanomaMiddle AgedQuinazolinesReceptor, IGF Type 1Skin NeoplasmsSoft Tissue NeoplasmsTaxoidsTreatment OutcomeConceptsAdvanced solid tumorsInsulin-like growth factor receptorType 1 insulin-like growth factor receptorGrowth factor receptorIGF-IISolid tumorsDisease controlCommon adverse eventsFactor receptorIGF-1R antibodyDurable disease controlCohort C2Adverse eventsPartial responseCohort BDocetaxel administrationSteroid premedicationControl ratePK interactionsGrade 3IGF-BP3Blood samplesCohort C1PatientsAVE1642
2011
Phase I dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy
Garrett C, Siu L, El-Khoueiry A, Buter J, Rocha-Lima C, Marshall J, LoRusso P, Major P, Chemidlin J, Mokliatchouk O, Velasquez L, Hayes W, Feltquate D, Syed S, Ford S, Kollia G, Galbraith S, Nuyten D. Phase I dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy. British Journal Of Cancer 2011, 105: 44-52. PMID: 21629245, PMCID: PMC3137402, DOI: 10.1038/bjc.2011.182.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlanineAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCetuximabDrug Therapy, CombinationFemaleGastrointestinal NeoplasmsHumansMaleMiddle AgedNeoplasm Recurrence, LocalSalvage TherapySurvival RateTissue DistributionTreatment OutcomeTriazinesVascular Endothelial Growth Factor Receptor-2ConceptsAdvanced gastrointestinal malignanciesGastrointestinal malignanciesPhase I dose-escalation studyAdvanced metastatic colorectal cancerCommon treatment-related toxicitiesMedian progression-free survivalI dose-escalation studyRadiographic partial responseMetastatic colorectal cancerTreatment-related toxicityAcceptable toxicity profileDose-escalation studyPhase III studyProgression-free survivalOverall response rateK-ras mutationsAcneiform dermatitisPrior therapyAdverse eventsIII studyMedian durationMucosal inflammationPartial responseCombination chemotherapyColorectal cancerDose-escalating and pharmacological study of bortezomib in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study
Leal T, Remick S, Takimoto C, Ramanathan R, Davies A, Egorin M, Hamilton A, LoRusso P, Shibata S, Lenz H, Mier J, Sarantopoulos J, Mani S, Wright J, Ivy S, Neuwirth R, von Moltke L, Venkatakrishnan K, Mulkerin D. Dose-escalating and pharmacological study of bortezomib in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study. Cancer Chemotherapy And Pharmacology 2011, 68: 1439-1447. PMID: 21479634, PMCID: PMC3481841, DOI: 10.1007/s00280-011-1637-5.Peer-Reviewed Original ResearchConceptsSevere renal dysfunctionNormal renal functionRenal dysfunctionAdult cancer patientsRenal functionDialysis patientsDose escalationCancer patientsPatient populationNational Cancer Institute Organ Dysfunction Working Group StudyDose of bortezomibImpaired renal functionGeneral patient populationIntravenous bortezomibRenal impairmentCreatinine clearanceModerate dysfunctionMild dysfunctionSevere dysfunctionDose reductionPharmacologic dataPatientsDay 1DysfunctionBortezomib
2010
A Phase I Study of the Pharmacokinetic and Safety Profiles of Oral Pazopanib With a High‐Fat or Low‐Fat Meal in Patients With Advanced Solid Tumors
Heath E, Chiorean E, Sweeney C, Hodge J, Lager J, Forman K, Malburg L, Arumugham T, Dar M, Suttle A, Gainer S, LoRusso P. A Phase I Study of the Pharmacokinetic and Safety Profiles of Oral Pazopanib With a High‐Fat or Low‐Fat Meal in Patients With Advanced Solid Tumors. Clinical Pharmacology & Therapeutics 2010, 88: 818-823. PMID: 20980999, DOI: 10.1038/clpt.2010.199.Peer-Reviewed Original ResearchConceptsHigh-fat mealAdvanced solid tumorsGrowth factor receptorSolid tumorsMaximum observed plasma concentrationPlasma concentration-time curvePhase IAdministration of pazopanibOral angiogenesis inhibitorVascular endothelial growth factor receptorFactor receptorEndothelial growth factor receptorLow-fat mealObserved plasma concentrationConcentration-time curvePlatelet-derived growth factor receptorDaily pazopanibOral pazopanibSafety profileSystemic exposureSingle doseSingle dosesPlasma concentrationsPazopanibFasted condition
2009
Phase I Dose-Escalation and Pharmacokinetic Study of Dasatinib in Patients with Advanced Solid Tumors
Demetri G, Russo P, MacPherson I, Wang D, Morgan J, Brunton V, Paliwal P, Agrawal S, Voi M, Evans T. Phase I Dose-Escalation and Pharmacokinetic Study of Dasatinib in Patients with Advanced Solid Tumors. Clinical Cancer Research 2009, 15: 6232-6240. PMID: 19789325, DOI: 10.1158/1078-0432.ccr-09-0224.Peer-Reviewed Original ResearchConceptsDose-limiting toxicitySolid tumorsHematologic toxicityFrequent treatment-related toxicitiesDurable stable diseaseGrade 2 proteinuriaGrade 2 rashGrade 3 fatigueGrade 3 hypocalcemiaGrade 3 lethargyGrade 3 nauseaI Dose-EscalationLess hematologic toxicityGrade 3 rashObjective tumor responsePhase II doseTreatment-related toxicityAdvanced solid tumorsDose-escalation studyMetastatic solid tumorsStandard therapy existsNontreatment daysStable diseaseDaily dosingStandard therapy
2008
Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group
Ramanathan R, Egorin M, Takimoto C, Remick S, Doroshow J, LoRusso P, Mulkerin D, Grem J, Hamilton A, Murgo A, Potter D, Belani C, Hayes M, Peng B, Ivy S. Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group. Journal Of Clinical Oncology 2008, 26: 563-569. PMID: 18235115, DOI: 10.1200/jco.2007.11.0304.Peer-Reviewed Original ResearchConceptsNausea/vomitingLiver dysfunctionLiver functionLD groupNational Cancer Institute Organ Dysfunction Working GroupLiver function test elevationsPlasma concentration-time curveD dose levelDose of imatinibDoses of imatinibSevere liver dysfunctionDose-limiting toxicityMild liver dysfunctionSerum total bilirubinNormal liver functionPharmacokinetics of imatinibDose-normalized areaConcentration-time curveConcentrations of imatinibImatinib doseAdvanced malignanciesImatinib exposureMaximal doseImatinib mesylateRenal excretion