2024
Phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with gastrointestinal (GI) cancers receiving FOLFOX chemotherapy with or without bevacizumab.
Noonan A, Schnell P, Trunzo D, Thornton W, Malalur P, Manne A, Abushahin L, Rahman S, Jin N, Hays J, Elkhatib R, Mittra A, Roychowdhury S, Lustberg M, Sparreboom A, Hu S. Phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with gastrointestinal (GI) cancers receiving FOLFOX chemotherapy with or without bevacizumab. Journal Of Clinical Oncology 2024, 42: 745-745. DOI: 10.1200/jco.2024.42.3_suppl.745.Peer-Reviewed Original ResearchOrganic cation transporter 2Serum biomarkersEfficacy biomarkersRecommended phase 2 doseRandomized phase II studySide effect of oxaliplatinRat dorsal root gangliaEarly study discontinuationMFOLFOX6 + bevacizumabPhase 2 doseStudy of dasatinibGastrointestinal (GI) cancersOxaliplatin-induced neuropathyPhase II studyEffect of oxaliplatinPhase I trialDose-finding studyLow intermittent dosesDorsal root gangliaDisabling side effectsDose of DAddition of DFOLFOX chemotherapyFOLFOX regimenStudy discontinuation
2023
A phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with gastrointestinal (GI) cancers receiving FOLFOX chemotherapy with or without bevacizumab.
Noonan A, Farid S, Schnell P, Trunzo D, Malalur P, Jin N, Manne A, Abushahin L, Rahman S, Hays J, Elkhatib R, Mittra A, Roychowdhury S, Lustberg M, Sparreboom A, Hu S. A phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with gastrointestinal (GI) cancers receiving FOLFOX chemotherapy with or without bevacizumab. Journal Of Clinical Oncology 2023, 41: e15613-e15613. DOI: 10.1200/jco.2023.41.16_suppl.e15613.Peer-Reviewed Original ResearchOrganic cation transporter 2Efficacy biomarkersRandomized phase II studyRat dorsal root gangliaAmount of oxaliplatinPhase 2 doseOxaliplatin-induced neuropathyPhase II studyPhase I trialDose-finding studyDorsal root gangliaLevels of biomarkersMajority of ptsFOLFOX chemotherapyFOLFOX regimenOX administrationII studyI trialPeripheral neuropathyGastrointestinal cancerGI cancersPreclinical dataRoot gangliaSerum biomarkersCohort 2
2020
Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice
Huang KM, Leblanc AF, Uddin ME, Kim JY, Chen M, Eisenmann ED, Gibson A, Li Y, Hong KW, DiGiacomo D, Xia S, Alberti P, Chiorazzi A, Housley SN, Cope TC, Sprowl JA, Wang J, Loprinzi CL, Noonan A, Lustberg M, Cavaletti G, Pabla N, Hu S, Sparreboom A. Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice. Journal Of Clinical Investigation 2020, 130: 4601-4606. PMID: 32484793, PMCID: PMC7456253, DOI: 10.1172/jci136796.Peer-Reviewed Original ResearchConceptsOrganic cation transporter 2Peripheral neurotoxicityColorectal cancerOxaliplatin-induced peripheral neurotoxicityOxaliplatin-containing therapyOxaliplatin-induced neurotoxicitySatellite glial cellsOxaliplatin neurotoxicityChronic formCancer patientsGlial cellsPreclinical modelsPreventive strategiesMouse modelPharmacological approachesPharmacological targetingTranslational significanceNeurotoxicityTransporter 2PatientsUptake transportersCancerAnticancer drugsCandidate transportersSolute carriersA phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer receiving FOLFOX chemotherapy and bevacizumab.
Noonan A, Lustberg M, Schnell P, Hays J, Jin N, Abushahin L, Malalur P, Roychowdhury S, Elkhatib R, Chen H, Al Mutar S, Sparreboom A, Hu S. A phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer receiving FOLFOX chemotherapy and bevacizumab. Journal Of Clinical Oncology 2020, 38: tps12125-tps12125. DOI: 10.1200/jco.2020.38.15_suppl.tps12125.Peer-Reviewed Original ResearchOxaliplatin-induced peripheral neuropathyOxaliplatin-induced neuropathyOrganic cation transporter 2Peripheral neuropathyColorectal cancerChronic oxaliplatin-induced peripheral neuropathyStage IV colorectal cancerRat dorsal root gangliaOxaliplatin-induced neurotoxicityPharmacokinetics of oxaliplatinPhase 2 doseMetastatic colorectal cancerPhase 1b trialDose-finding studyDorsal root gangliaAddition of dasatinibQuality of lifeSmall molecule kinase inhibitorsFOLFOX chemotherapyOral dasatinibBevacizumab therapyRoot gangliaSerum biomarkersIntermittent doseRat model