Anticancer agent - vandetanib
For a tumour to survive, it has to develop its own blood supply so that it can acquire nutrients and oxygen.
For a tumour to survive, it has to develop its own blood supply so that it can acquire nutrients and oxygen.
It does this by the process of angiogenesis - the formation of blood vessels. This process is essential for tumour growth, and also plays a role in the development of metastases.
Preventing tumour angiogenesis has received much attention in drug discovery in recent years, with numerous different targets being investigated. These include vascular endothelial growth factor, or VEGF, which is upregulated in tumours, and acts at a variety of different receptors.
One of these, VEGFR2, is the target of a new drug being developed by AstraZeneca. Vandetanib, formerly known as ZD 6474, is an orally active VEGFR2 inhibitor, which also has some activity at a couple of other EGF receptor types.1
A dose escalating Phase I trial was carried out on patients with a variety of different solid tumours, including breast cancer and melanoma.2 They were given a single dose of the drug, and after a seven day observation period were given daily oral doses for continuous cycles of 28 days. Two patients - one with gastrointestinal stromal tumour, and the other melanoma - achieved stable disease after 156 days.
In a further Phase I study, 18 patients with refractory solid tumours were given a single oral dose of 100, 200, 300 or 400mg, and after a seven day observation period were given the same dose every day for a further 28 days.3 They were given further 28-day cycles without interruption. Four patients with non-small cell lung cancer experienced tumour regression, and doses up to 300mg were well tolerated.
A two part randomised Phase II trial has been carried out: the first part investigates the safety and efficacy of a combination of the drug with docetaxel, plus any pharmacokinetic interactions.4 In the open label first phase, patients with locally advanced or metastatic NSCLC who had failed first line platinum therapy were given 75mg/m2 docetaxel every 21 days and100mg vandetanib once a day. If there was no dose limiting toxicity by week four, the next cohort was given a higher dose, 300mg, of vandetanib. A reversible rash was the most common side effect. Trials continue.