2021
Ceralasertib-Mediated ATR Inhibition Combined With Olaparib in Advanced Cancers Harboring DNA Damage Response and Repair Alterations (Olaparib Combinations)
Mahdi H, Hafez N, Doroshow D, Sohal D, Keedy V, T. K, LoRusso P, Jürgensmeier J, Avedissian M, Sklar J, Glover C, Felicetti B, Dean E, Mortimer P, Shapiro GI, Eder JP. Ceralasertib-Mediated ATR Inhibition Combined With Olaparib in Advanced Cancers Harboring DNA Damage Response and Repair Alterations (Olaparib Combinations). JCO Precision Oncology 2021, 5: 1432-1442. PMID: 34527850, PMCID: PMC8437220, DOI: 10.1200/po.20.00439.Peer-Reviewed Original ResearchConceptsHigh-grade serous ovarian cancerComplete responseResponse rateClinical benefit ratePartial response ratePrimary end pointOverall response rateHomologous recombination repair deficiencySerous ovarian cancerPoly (ADP-ribose) polymerase (PARP) inhibitorsPrior therapyUnacceptable toxicityEntire cohortRefractory cancerBenefit rateOvarian cancerPromising therapyPatientsBasket trialsDay 1End pointOlaparibPolymerase inhibitorsTherapyAdditional studiesIdentifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial
LoRusso PM, Sekulic A, Sosman JA, Liang WS, Carpten J, Craig DW, Solit DB, Bryce AH, Kiefer JA, Aldrich J, Nasser S, Halperin R, Byron SA, Pilat MJ, Boerner SA, Durecki D, Hendricks WPD, Enriquez D, Izatt T, Keats J, Legendre C, Markovic SN, Weise A, Naveed F, Schmidt J, Basu GD, Sekar S, Adkins J, Tassone E, Sivaprakasam K, Zismann V, Calvert VS, Petricoin EF, Fecher LA, Lao C, Eder JP, Vogelzang NJ, Perlmutter J, Gorman M, Manica B, Fox L, Schork N, Zelterman D, DeVeaux M, Joseph RW, Cowey CL, Trent JM. Identifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial. PLOS ONE 2021, 16: e0248097. PMID: 33826614, PMCID: PMC8026051, DOI: 10.1371/journal.pone.0248097.Peer-Reviewed Original ResearchConceptsMetastatic melanomaAlternate treatment armResponse-evaluable patientsMetastatic melanoma patientsComprehensive genomic profilingAdditional drug classesCutaneous metastatic melanomaLack of responseCombination BRAFStable diseaseTwo-stage optimal designPartial responseProgressive diseaseCare therapyMelanoma patientsMelanoma TrialTreatment armsTreatment optionsBRAFV600 mutationsClinical trialsDrug classesResponse ratePatientsDrug selectionMelanomaClinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas
Eder JP, Doroshow DB, T. K, Keedy VL, Sklar JS, Glazer P, Bindra R, Shapiro GI. Clinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas. JCO Precision Oncology 2021, 5: 466-472. PMID: 34994649, PMCID: PMC9848565, DOI: 10.1200/po.20.00247.Peer-Reviewed Original ResearchConceptsPulmonary epithelioid hemangioendotheliomaStable diseaseEpithelioid hemangioendotheliomaClinical benefitClinical benefit rateOpen-label studyPrimary end pointPoly (ADP-ribose) polymerase inhibitionDefective homologous recombination (HR) repairMesenchymal sarcomaObjective responsePartial responseClinical efficacyPatient populationBenefit rateCombination trialsPatientsSolid tumorsIDH1/2-mutant tumorsIDH1/2 mutationsPARP inhibitorsEnd pointPARP inhibitionTumorsOlaparib
2014
New Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs
Jürgensmeier JM, Eder JP, Herbst RS. New Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs. Clinical Cancer Research 2014, 20: 4425-4435. PMID: 25183480, PMCID: PMC5369358, DOI: 10.1158/1078-0432.ccr-13-0753.Peer-Reviewed Original ResearchConceptsClinical trialsTumor biologyFuture patient selectionTherapy of patientsOngoing clinical evaluationBroad molecular profilingPromising tumor targetPersonalized medicinePatient selectionPatient populationTreatment recommendationsClinical evaluationTumor boardClinical studiesImmune parametersNovel agentsTumor targetsTreatment approachesSolid tumorsClinical researchPatientsMolecular profilingSpecific markersTumorsTrials
2005
Proteasome Inhibition With Bortezomib (PS-341): A Phase I Study With Pharmacodynamic End Points Using a Day 1 and Day 4 Schedule in a 14-Day Cycle
Hamilton AL, Eder JP, Pavlick AC, Clark JW, Liebes L, Garcia-Carbonero R, Chachoua A, Ryan DP, Soma V, Farrell K, Kinchla N, Boyden J, Yee H, Zeleniuch-Jacquotte A, Wright J, Elliott P, Adams J, Muggia FM. Proteasome Inhibition With Bortezomib (PS-341): A Phase I Study With Pharmacodynamic End Points Using a Day 1 and Day 4 Schedule in a 14-Day Cycle. Journal Of Clinical Oncology 2005, 23: 6107-6116. PMID: 16135477, DOI: 10.1200/jco.2005.01.136.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityDay 1Main dose-limiting toxicityPhase IGrade 3 thrombocytopeniaPhase II doseCell lung cancerPharmacodynamic end pointsRenal cell carcinomaProteasome activityNovel antineoplastic agentPartial responseCell carcinomaLung cancerToxicity profileWeek scheduleAntitumor effectsDose levelsPatientsSolid tumorsTotal doseHigh dosesTotal dosesNeurotoxic agentsBaseline activity
1989
A phase I clinical and pharmacokinetic study of carboplatin and autologous bone marrow support.
Shea TC, Flaherty M, Elias A, Eder JP, Antman K, Begg C, Schnipper L, Frei E, Henner WD. A phase I clinical and pharmacokinetic study of carboplatin and autologous bone marrow support. Journal Of Clinical Oncology 1989, 7: 651-61. PMID: 2651580, DOI: 10.1200/jco.1989.7.5.651.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseAutologous bone marrow reinfusionAutologous bone marrow supportBone marrow reinfusionBone marrow supportMarrow reinfusionMarrow supportSystemic clearancePhase IConsiderable dose escalationRecurrent ovarian cancerPharmacokinetic studySevere ototoxicityToxicity consistingRenal dysfunctionDose escalationReversible hepatotoxicityContinuous infusionOvarian cancerActive drugHigh dosesLow dosesCarboplatinPatientsDoses
1988
Malignant melanoma. Treatment with high-dose combination alkylating agent chemotherapy and autologous bone marrow support.
Shea TC, Antman KH, Eder JP, Elias A, Peters WP, Schryber S, Henner WD, Schoenfeld DA, Schnipper LE, Frei E. Malignant melanoma. Treatment with high-dose combination alkylating agent chemotherapy and autologous bone marrow support. JAMA Dermatology 1988, 124: 878-84. PMID: 3288124, DOI: 10.1001/archderm.124.6.878.Peer-Reviewed Original ResearchConceptsAutologous bone marrow supportBone marrow supportHigh-dose combinationMarrow supportAgent chemotherapyPhase 2 doseMetastatic malignant melanomaOverall response rateMedian survivalComplete responsePartial responseSurgical resectionAdditional patientsMedian timeResidual tumorTreatment courseMalignant melanomaMarrow reconstitutionChemotherapyToxic reactionsPatientsResponse rateEntire groupMonthsDisease