2006
A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas
Duran I, Kortmansky J, Singh D, Hirte H, Kocha W, Goss G, Le L, Oza A, Nicklee T, Ho J, Birle D, Pond G, Arboine D, Dancey J, Aviel-Ronen S, Tsao M, Hedley D, Siu L. A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. British Journal Of Cancer 2006, 95: 1148-1154. PMID: 17031397, PMCID: PMC2360568, DOI: 10.1038/sj.bjc.6603419.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsCarcinoid TumorCarcinoma, NeuroendocrineDisease ProgressionExanthemaFatigueFemaleFollow-Up StudiesHumansHyperglycemiaInfusions, IntravenousMaleMiddle AgedPancreatic NeoplasmsPhosphorylationProtein KinasesProto-Oncogene Proteins c-aktRibosomal Protein S6SirolimusSurvival AnalysisTOR Serine-Threonine KinasesTreatment OutcomeConceptsAdvanced neuroendocrine carcinomaNeuroendocrine carcinomaAdverse eventsOverall survivalFrequent drug-related adverse eventsDrug-related adverse eventsRash/desquamationTreat response ratePhase II studyPercentage of patientsHigher baseline levelsII studyWeekly dosesNeuroendocrine tumorsTumor responsePharmacodynamic analysisPharmacodynamic studiesTumor biopsiesTemsirolimusResponse rateBaseline levelsPatientsPathway downregulationArchival specimensPhosphorylation of S6
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