2023
Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Cecchini M, Zhang J, Wei W, Sklar J, Lacy J, Zhong M, Kong Y, Zhao H, DiPalermo J, Devine L, Stein S, Kortmansky J, Johung K, Bindra R, LoRusso P, Schalper K. Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer. Cancer Research Communications 2023, 3: 1132-1139. PMID: 37387791, PMCID: PMC10305782, DOI: 10.1158/2767-9764.crc-23-0045.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMGMT protein expressionColorectal cancerStable diseaseQuantitative immunofluorescenceT cellsProtein expressionPromoter hypermethylationLow MGMT protein expressionPARP inhibitorsRadiographic tumor regressionMetastatic colorectal cancerAdvanced colorectal cancerPretreatment tumor biopsiesEffector T cellsTumor-infiltrating lymphocytesMGMT proteinDNA repair biomarkersBaseline CD8Eligible patientsIncreased CD8Methylguanine-DNA methyltransferaseObjective responseProgressive diseaseImmune markers
2009
A Phase II Study of Flavopiridol (Alvocidib) in Combination with Docetaxel in Refractory, Metastatic Pancreatic Cancer
Carvajal RD, Tse A, Shah MA, Lefkowitz RA, Gonen M, Gilman-Rosen L, Kortmansky J, Kelsen DP, Schwartz GK, O'Reilly E. A Phase II Study of Flavopiridol (Alvocidib) in Combination with Docetaxel in Refractory, Metastatic Pancreatic Cancer. Pancreatology 2009, 9: 404-409. PMID: 19451750, PMCID: PMC4053191, DOI: 10.1159/000187135.Peer-Reviewed Original ResearchConceptsPhase II studyPancreatic adenocarcinomaII studyRisk/benefit equationGrade 3 diarrheaGrade 3 fatigueTransient stable diseaseGrade 4 neutropeniaMetastatic pancreatic adenocarcinomaMetastatic pancreatic cancerCombination of flavopiridolCell cycle dysregulationPrimary endpointStable diseaseMedian survivalObjective responseAdverse eventsPatient populationTumor sizePan-cyclinPancreatic cancerClinical activityTumor measurementsDose reductionPatients
2005
Phase I Trial of the Cyclin-Dependent Kinase Inhibitor and Protein Kinase C Inhibitor 7-Hydroxystaurosporine in Combination With Fluorouracil in Patients With Advanced Solid Tumors
Kortmansky J, Shah MA, Kaubisch A, Weyerbacher A, Yi S, Tong W, Sowers R, Gonen M, O'Reilly E, Kemeny N, Ilson DI, Saltz LB, Maki RG, Kelsen DP, Schwartz GK. Phase I Trial of the Cyclin-Dependent Kinase Inhibitor and Protein Kinase C Inhibitor 7-Hydroxystaurosporine in Combination With Fluorouracil in Patients With Advanced Solid Tumors. Journal Of Clinical Oncology 2005, 23: 1875-1884. PMID: 15699481, DOI: 10.1200/jco.2005.03.116.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsMononuclear cellsPlasma concentrationsProtein kinase C inhibitorMean maximal plasma concentrationUCN-01Kinase C inhibitorPhase I clinical trialPhase II doseAdvanced solid tumorsPhase II trialMaximal plasma concentrationSignificant interpatient variabilityReverse transcriptase-polymerase chain reactionAlpha-1-acid glycoproteinC inhibitorFibonacci designFU dosePrior fluoropyrimidinesStable diseaseCyclin-dependent kinase inhibitorII trialObjective responseWeekly infusionsI trial