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
A Phase I Clinical Trial of the Sequential Combination of Irinotecan Followed by Flavopiridol
Shah MA, Kortmansky J, Motwani M, Drobnjak M, Gonen M, Yi S, Weyerbacher A, Cordon-Cardo C, Lefkowitz R, Brenner B, O'Reilly E, Saltz L, Tong W, Kelsen DP, Schwartz GK. A Phase I Clinical Trial of the Sequential Combination of Irinotecan Followed by Flavopiridol. Clinical Cancer Research 2005, 11: 3836-3845. PMID: 15897584, DOI: 10.1158/1078-0432.ccr-04-2651.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBilirubinCamptothecinCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p21Drug Administration ScheduleDrug InteractionsFemaleFlavonoidsHumansIntracellular Signaling Peptides and ProteinsIrinotecanMaleMaximum Tolerated DoseMiddle AgedNeoplasmsPiperidinesTreatment OutcomeTumor Suppressor Protein p53ConceptsCombination therapyCycle 1 dose-limiting toxicitiesPhase I clinical trialDose-limiting diarrheaPhase II dosePosttreatment tumor biopsiesSignificant pharmacokinetic interactionsAdvanced solid tumorsDose-limiting toxicityPhase I trialBaseline serum bilirubinColorectal cancer xenograftsWild-type p53 tumorsMumol/LBaseline bilirubinFlavopiridol concentrationsStable diseasePartial responseI trialPharmacokinetic interactionsSerum bilirubinDifferentiation-related gene-1Responsive diseaseHepatocellular cancerCancer xenografts
2003
The cyclin-dependent kinase inhibitor flavopiridol potentiates gamma-irradiation-induced apoptosis in colon and gastric cancer cells.
Jung C, Motwani M, Kortmansky J, Sirotnak FM, She Y, Gonen M, Haimovitz-Friedman A, Schwartz GK. The cyclin-dependent kinase inhibitor flavopiridol potentiates gamma-irradiation-induced apoptosis in colon and gastric cancer cells. Clinical Cancer Research 2003, 9: 6052-61. PMID: 14676132.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisCaspase 3CaspasesCell DivisionColonic NeoplasmsCyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsCytochromes cEnzyme ActivationEnzyme InhibitorsFlavonoidsGamma RaysMaleMiceMice, NudeMicroscopy, FluorescencePiperidinesPoly(ADP-ribose) PolymerasesStomach NeoplasmsTransplantation, HeterologousTumor Cells, CulturedConceptsEffect of flavopiridolHCT-116 cellsMKN-74Single agentInduction of apoptosisParental HCT-116 cellsAdvanced gastrointestinal cancerTumor-bearing animalsCyclin-dependent kinase inhibitor flavopiridolEfficacy of combinationNational Cancer InstituteMKN-74 cellsGastric cancer cellsP21 protein expressionKinase inhibitor flavopiridolAdjuvant treatmentCyclin-dependent kinase inhibitorLoss of p21HCT-116Gastrointestinal cancerTumor regressionCancer cell line HCT-116Human colon cancer cell line HCT-116Gastric cancerCancer Institute