2023
Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Sacher A, LoRusso P, Patel M, Miller W, Garralda E, Forster M, Santoro A, Falcon A, Kim T, Paz-Ares L, Bowyer S, de Miguel M, Han S, Krebs M, Lee J, Cheng M, Arbour K, Massarelli E, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Dharia N, Schutzman J, Desai J. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. New England Journal Of Medicine 2023, 389: 710-721. PMID: 37611121, DOI: 10.1056/nejmoa2303810.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalTreatment-related adverse eventsProgression-free survivalAdverse eventsSolid tumorsG12C mutationLow-grade adverse eventsGrade 3 eventsGrade 4 eventsTreatment-related deathsDiscontinuation of treatmentMetastatic solid tumorsPhase 1 studyDurable clinical responsesBiomarkers of responseKRAS G12C mutationAssessment of safetyVariant allele frequencyClinical responseColorectal cancerSerial assessmentDose reductionG12C inhibitorsPatientsTumor DNA
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
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 excretionPhase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Renal Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group
Gibbons J, Egorin M, Ramanathan R, Fu P, Mulkerin D, Shibata S, Takimoto C, Mani S, LoRusso P, Grem J, Pavlick A, Lenz H, Flick S, Reynolds S, Lagattuta T, Parise R, Wang Y, Murgo A, Ivy S, Remick S. Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Renal Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group. Journal Of Clinical Oncology 2008, 26: 570-576. PMID: 18235116, DOI: 10.1200/jco.2007.13.3819.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseSerious adverse eventsDose-limiting toxicityImatinib dosesGroup patientsRenal dysfunctionImatinib exposureNormal groupNational Cancer Institute Organ Dysfunction Working GroupAlpha-1-acid glycoprotein concentrationSerum alpha-1-acid glycoprotein concentrationsMild group patientsRenal dysfunction groupModerate renal dysfunctionAdvanced solid tumorsPharmacokinetics of imatinibAcid glycoprotein concentrationPlasma AGP concentrationImatinib clearanceImatinib dosePlasma imatinibStable diseaseDysfunction groupRenal impairmentAdult patients
2002
Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition.
Albanell J, Rojo F, Averbuch S, Feyereislova A, Mascaro J, Herbst R, LoRusso P, Rischin D, Sauleda S, Gee J, Nicholson R, Baselga J. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. Journal Of Clinical Oncology 2002, 20: 110-24. PMID: 11773160, DOI: 10.1200/jco.2002.20.1.110.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntineoplastic AgentsApoptosisBiomarkersCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p27Dose-Response Relationship, DrugErbB ReceptorsFemaleGefitinibHumansKeratinocytesMaleMAP Kinase Signaling SystemMiddle AgedNeoplasmsQuinazolinesSkinStatistics, NonparametricTumor Suppressor ProteinsConceptsCancer patientsEpidermal growth factor receptor tyrosine kinase inhibitor ZD1839Tyrosine kinase inhibitor ZD1839Phase I clinical trialMaximum-tolerated doseDose-limiting toxicityEGFR activationReceptor-dependent processUnacceptable toxicityDefinitive efficacyPharmacodynamic assessmentSafety trialPharmacodynamic effectsClinical trialsKeratin plugsReceptor inhibitionMaturation markersSkin biopsiesPharmacodynamic studiesProliferation indexDose levelsOral ZD1839PatientsOptimal dosesZD1839
2001
Multicenter, Phase II study of capecitabine in taxane‐pretreated metastatic breast carcinoma patients
Blum J, Dieras V, Russo P, Horton J, Rutman O, Buzdar A, Osterwalder B. Multicenter, Phase II study of capecitabine in taxane‐pretreated metastatic breast carcinoma patients. Cancer 2001, 92: 1759-1768. PMID: 11745247, DOI: 10.1002/1097-0142(20011001)92:7<1759::aid-cncr1691>3.0.co;2-a.Peer-Reviewed Original ResearchConceptsMetastatic breast carcinomaTreatment-related adverse eventsHand-foot syndromeBreast carcinomaAdverse eventsGrade 3 treatment-related adverse eventsCommon treatment-related adverse eventsResponse rateGrade 4 adverse eventsMetastatic breast carcinoma patientsPrevious chemotherapy regimensPrior anthracycline chemotherapyTreatment-related deathsPhase II studyPhase II trialBreast carcinoma patientsSubgroup of patientsOverall response rateCurrent multicenterFluoropyrimidine carbamateOral capecitabineAnthracycline chemotherapyChemotherapy regimensII trialTaxane therapyChronic Oral Administration of CI-994: A Phase I Study
Prakash S, Foster B, Meyer M, Wozniak A, Heilbrun L, Flaherty L, Zalupski M, Radulovic L, Valdivieso M, LoRusso P. Chronic Oral Administration of CI-994: A Phase I Study. Investigational New Drugs 2001, 19: 1-11. PMID: 11291827, DOI: 10.1023/a:1006489328324.Peer-Reviewed Original ResearchConceptsHuman tumor xenograftsCI-994Dosing phaseStable diseaseTumor xenograftsNon-small cell lungNovel oral agentsChronic oral administrationDaily oral dosePeak plasma levelsRat leukemia modelOral agentsStarting doseDosage escalationGastrointestinal effectsDaily administrationOral doseCell lungPlasma levelsSingle dosesOral administrationRenal cancerChronic basisFood intakeTreatment duration