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dc.contributor.authorBlackhall, Fiona H
dc.contributor.authorO'Brien, Mary
dc.contributor.authorSchmid, Peter
dc.contributor.authorNicolson, Marianne
dc.contributor.authorTaylor, Paul
dc.contributor.authorMilenkova, Tsveta
dc.contributor.authorKennedy, Sarah J
dc.contributor.authorThatcher, Nick
dc.date.accessioned2010-09-14T12:00:32Z
dc.date.available2010-09-14T12:00:32Z
dc.date.issued2010-08
dc.identifier.citationA phase I study of Vandetanib in combination with vinorelbine/cisplatin or gemcitabine/cisplatin as first-line treatment for advanced non-small cell lung cancer. 2010, 5 (8):1285-8 J Thorac Oncolen
dc.identifier.issn1556-1380
dc.identifier.pmid20661087
dc.identifier.doi10.1097/JTO.0b013e3181e3a2d1
dc.identifier.urihttp://hdl.handle.net/10541/111156
dc.description.abstractINTRODUCTION: Vandetanib is a once-daily oral agent that selectively inhibits vascular endothelial growth factor receptor, epidermal growth factor receptor, and RET (REarranged during Transfection) signaling. METHODS: This Phase I study investigated the safety, tolerability, and pharmacokinetics of vandetanib when administered with either gemcitabine plus cisplatin (GC) or vinorelbine plus cisplatin (VC) in patients with previously untreated locally advanced or metastatic non-small cell lung cancer. RESULTS: Seventeen patients received vandetanib 100 mg/d plus VC (n = 9) or GC (n = 8). Three dose-limiting toxicities were reported in each treatment group: vandetanib + VC (pulmonary artery thrombosis and asymptomatic QTc prolongation [n = 2]); vandetanib + GC (peripheral ischemia [due to arterial occlusion], pulmonary embolism, and limb venous thrombosis). The protocol definition of a tolerable dose was not met, and no patients were recruited to receive vandetanib 300 mg plus VC or GC. There was no apparent pharmacokinetic interaction between vandetanib and vinorelbine or gemcitabine, but there was an approximate 30% increase in the exposure to cisplatin, which may be due to accumulation of total platinum and/or an interaction with vandetanib. CONCLUSIONS: In this study, in patients with previously untreated advanced non-small cell lung cancer, vandetanib 100 mg/d in combination with either VC or GC was not tolerated.
dc.language.isoenen
dc.subjectLung Canceren
dc.subjectVandetaniben
dc.titleA phase I study of Vandetanib in combination with vinorelbine/cisplatin or gemcitabine/cisplatin as first-line treatment for advanced non-small cell lung cancer.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom. Fiona.Blackhall@christie.nhs.uken
dc.identifier.journalJournal of Thoracic Oncologyen
html.description.abstractINTRODUCTION: Vandetanib is a once-daily oral agent that selectively inhibits vascular endothelial growth factor receptor, epidermal growth factor receptor, and RET (REarranged during Transfection) signaling. METHODS: This Phase I study investigated the safety, tolerability, and pharmacokinetics of vandetanib when administered with either gemcitabine plus cisplatin (GC) or vinorelbine plus cisplatin (VC) in patients with previously untreated locally advanced or metastatic non-small cell lung cancer. RESULTS: Seventeen patients received vandetanib 100 mg/d plus VC (n = 9) or GC (n = 8). Three dose-limiting toxicities were reported in each treatment group: vandetanib + VC (pulmonary artery thrombosis and asymptomatic QTc prolongation [n = 2]); vandetanib + GC (peripheral ischemia [due to arterial occlusion], pulmonary embolism, and limb venous thrombosis). The protocol definition of a tolerable dose was not met, and no patients were recruited to receive vandetanib 300 mg plus VC or GC. There was no apparent pharmacokinetic interaction between vandetanib and vinorelbine or gemcitabine, but there was an approximate 30% increase in the exposure to cisplatin, which may be due to accumulation of total platinum and/or an interaction with vandetanib. CONCLUSIONS: In this study, in patients with previously untreated advanced non-small cell lung cancer, vandetanib 100 mg/d in combination with either VC or GC was not tolerated.


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