2020
Development 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 inhibition
2015
Phase I study of ABT-700, an anti-c-Met antibody, in patients (pts) with advanced gastric or esophageal cancer (GEC).
Kang Y, LoRusso P, Salgia R, Yen C, Lin C, Ramanathan R, Kaminker P, Sokolova I, Bhathena A, Wang L, Naumovski L, Strickler J. Phase I study of ABT-700, an anti-c-Met antibody, in patients (pts) with advanced gastric or esophageal cancer (GEC). Journal Of Clinical Oncology 2015, 33: 167-167. DOI: 10.1200/jco.2015.33.3_suppl.167.Peer-Reviewed Original ResearchAnti-c-Met antibodySingle-agent activityMET amplificationProgressive diseasePartial responseSubstantial single-agent activityGood responsePrimary untreated tumorsRECIST version 1.1Treatment-refractory tumorsDose-escalation phaseHuman xenograft tumorsC-Met overexpressionPrimary tumor tissuesTumor biopsy tissueLonger PFSAdvanced gastricAdverse eventsPrior linesSystemic therapyRecurrent tumorsPatient populationEsophageal cancerPrimary tumorEscalation phase
2011
Dose-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