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A phase I study of Vandetanib in combination with vinorelbine/cisplatin or gemcitabine/cisplatin as first-line treatment for advanced non-small cell lung cancer.
- Source :
-
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2010 Aug; Vol. 5 (8), pp. 1285-8. - Publication Year :
- 2010
-
Abstract
- Introduction: 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.<br />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.<br />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.<br />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.
- Subjects :
- Adult
Aged
Antineoplastic Combined Chemotherapy Protocols pharmacokinetics
Brain Neoplasms secondary
Carcinoma, Non-Small-Cell Lung pathology
Carcinoma, Squamous Cell pathology
Cisplatin administration & dosage
Deoxycytidine administration & dosage
Deoxycytidine analogs & derivatives
Female
Humans
Lung Neoplasms pathology
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Staging
Piperidines administration & dosage
Quinazolines administration & dosage
Survival Rate
Tissue Distribution
Treatment Outcome
Vinblastine administration & dosage
Vinblastine analogs & derivatives
Vinorelbine
Gemcitabine
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Brain Neoplasms drug therapy
Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Squamous Cell drug therapy
Lung Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1556-1380
- Volume :
- 5
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 20661087
- Full Text :
- https://doi.org/10.1097/JTO.0b013e3181e3a2d1