Drug therapies that focus on the vascular endothelial growth factor (VEGF) in treating advanced or metastasised cancer represents a huge slice of drug treatments currently in development. This molecular target paves the way for a therapeutic method that blocks the growth of tumours with minimal side effects.
VEGF is a naturally occurring protein in the body whose normal role is to trigger formation of new blood vessels (angiogenesis) to support the growth of the body's tissues and organs. It has also been associated with the abnormal growth of new blood vessels surrounding tumours to support their expansion.
At the American Society of Clinical Oncology meeting, taking place this week in New Orleans, several companies presented data on drug candidates aiming to tackle cancer by blocking VEGF.
US biopharmaceutical company, Regeneron Pharmaceuticals , announced positive preliminary results from a Phase I trial of VEGF Trap in patients with advanced solid tumours. Preclinical studies have demonstrated that the VEGF Trap is a potent blocker of VEGF.
The study was an open label, dose-escalation trial. Subcutaneous injections were given to 38 patients with 15 different types of incurable, relapsed or refractory solid tumour.
Initial results revealed that VEGF Trap was well-tolerated at the dose levels studied, suggesting the maximum tolerated dose has not been reached, The majority of adverse events were mild to moderate and similar to effects seen in clinical trials of anti-angiogenesis agents.
Vasgene Therapeutics demonstrated in a Phase I trial that its VEGF-AS (Veglin) lowers levels of the growth factor and has shown safety in patients with a wide variety of cancers. Veglin has also shown the ability to periodically stabilise or reduce tumours in additional human clinical trials.
An antisense oligonucleotide, Veglin binds directly to the gene that produces VEGF with the intent to block VEGF production.
VasGene anticipates initiating multi-centre Phase II clinical trials during the third quarter of 2004 for patients with renal cell carcinoma, mesothelioma, leukemia and lymphoma.
Pharmaceutical giant, Bayer and Onyx Pharmaceuticals, announced interim results from a Phase l/II clinical trial of BAY 43-9006 administered in combination with the chemotherapeutic agents carboplatin and paclitaxel to treat patients with advanced malignant melanoma.
BAY 43-9006, a novel RAF kinase and VEGFR inhibitor, is under investigation for the prevention of tumour growth, exerted an antiangiogenic effect by targeting the receptor tyrosine kinases VEGFR-2 and PDGFR and their associated signaling cascade.
35 sufferers of metastatic melanoma participanted in the study. 83 per cent observed tumour shrinkage (40 per cent) or disease stabilisation (43 per cent) when treated with BAY 43-9006 plus carboplatin and paclitaxel. Fourteen participants (40 per cent) had tumour shrinkage of 50 per cent or greater, lasting for six months or more. 15 participants (43 per cent) had disease stabilisation.
The new stable of anti-VEGF therapies are treading ground already covered by Genentech which is currently pursuing a broad late-stage clinical development program with Avastin (bevacizumab), evaluating its potential use in multiple tumour types. Phase III clinical trials in renal cell carcinoma, advanced non-small cell lung cancer, and metastatic breast cancer are being conducted with plans for pivotal trials in adjuvant colorectal cancer and metastatic & locally advanced pancreatic cancer.
Avastin is a recombinant humanised antibody to that binds to and inhibits VEGF. It was granted its first approval - by the US Food and Drug Administration (FDA) - on February 26. It is indicated for use in combination with intravenous 5-fluorouracil-based chemotherapy as a treatment for first-line metastatic colorectal cancer.