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

Blackhall, Fiona H, O'brien, Mary, Schmid, Peter, Nicolson, Marianne, Taylor, Paul, Milenkova, Tsveta, Kennedy, Sarah J and Thatcher, Nick (2010) 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. Journal of Thoracic Oncology, 5 (8). pp. 1285-1288. ISSN 1556-1380

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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.

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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: R Medicine
R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology Including cancer and carcinogens
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology Including cancer and carcinogens > RC0280 By region, system, or organ of the body, or type of tumor, A-Z > RC0280.B8 Breast. Mammary glands
Depositing User: Tracey O'Gorman
Date Deposited: 01 Nov 2012 15:24
Last Modified: 14 May 2015 09:42
URI: http://sro.sussex.ac.uk/id/eprint/41310
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