2019
Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial
Eng C, Kim T, Bendell J, Argilés G, Tebbutt N, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal N, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F, Investigators I, Ahn J, Asselah J, Badarinath S, Baijal S, Begbie S, Berry S, Canon J, Carbone R, Cervantes A, Cha Y, Chang K, Chaudhry A, Chmielowska E, Cho S, Chu D, Couture F, Cultrera J, Cunningham D, Van Cutsem E, Cuyle P, Davies J, Dowden S, Dvorkin M, Ganju V, Garcia R, Kerr R, Kim T, King K, Kortmansky J, Kozloff M, Lam K, Lee J, Lee A, Lesperance B, Luppi G, Ma B, Maiello E, Mandanas R, Marshall J, Marx G, Mullamitha S, Nechaeva M, Park J, Pavlakis N, Ponce C, Potemski P, Raouf S, Reeves J, Segal N, Siena S, Smolin A, Streb J, Strickland A, Szutowicz-Zielinska E, Tabernero J, Tan B, Valera J, Van den Eynde M, Vergauwe P, Vickers M, Womack M, Wroblewska M, Young R. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. The Lancet Oncology 2019, 20: 849-861. PMID: 31003911, DOI: 10.1016/s1470-2045(19)30027-0.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerMicrosatellite-stable metastatic colorectal cancerRegorafenib groupOverall survivalColorectal cancerAdverse eventsCombination groupAtezolizumab groupAtezolizumab monotherapyOpen-labelBaseline Eastern Cooperative Oncology Group performance statusEndpoint of improving overall survivalEastern Cooperative Oncology Group performance statusAll-cause grade 3Increased blood creatine phosphokinaseTreat metastatic colorectal cancerIntention-to-treat populationControlled trialsSafety of atezolizumabSystemic chemotherapy regimensThird-line settingMedian overall survivalTreatment-related deathsImmunotherapy to patientsMedian follow-up
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