Summary

Angiogenesis is the growth of new blood vessels to supply a tumor and it is the latest target of cancer therapy. Addition of a new anti-angiogenesis drug, axitinib, to conventional chemotherapy has now been trialled in patients with advanced pancreatic cancer. This Phase II study demonstrated the safety of this approach and also showed that combination therapy led to a modest improvement in survival.

Introduction

Pancreatic cancer accounts for around quarter of a million deaths around the world every year and is the eighth most-common form of cancer-related death. In North America, pancreatic cancer is the fourth most common form of cancer death, with 37,700 new cases and 33,300 deaths in 2008. The five year survival rate is shockingly low at only five percent.

The standard therapy for pancreatic cancer is a drug called gemcitabine, but it appears to give the patient little survival benefit. It has been trialled, recently, in combination with other drugs but here, too, results have been disappointing. Therefore there is an urgent need for new approaches to the treatment of pancreatic cancer.

As tumors grow, they develop a new blood supply - a process called angiogenesis. There is much interest now in 'starving' a tumor by targeting the angiogenesis process. Some of the anti-angiogenesis agents work by targeting a key molecule in angiogenesis called vascular endothelial growth factor (VEGF). One of these, bevacizumab, has already been tried in advanced pancreatic cancer but did not show a survival advantage over gemcitabine. But other VEGF inhibitors might be more impressive. Accordingly, Jean-Philippe Spano of the Hôpital de la Pitié Salpêtrière in Paris carried out a Phase II clinical trial with axitinib, a potent and selective oral drug that inhibits VEGF receptors.

What was done

A group of 103 patients with inoperable, locally advanced or metastatic pancreatic cancer received either gemcitabine alone or gemcitabine with axitinib. The researchers measured overall survival.

What was found

Median overall survival time was 6.9 months among those on combination therapy, compared to 5.6 months for gemcitabine alone. The safety profile of combination therapy was similar to that of gemcitabine alone.

What this study means

The gain in survival time by adding axitinib to gemcitabine was small. In fact, it did not even reach statistical significance. Patients who had local disease tended to survive for longer. The finding that axitinib does not show any adverse effects when combined with gemcitabine is promising. Phase III studies, involving more patients, will show more about what survival gains can be expected from axitinib. It may do better when administered earlier on in the disease process. Targeting angiogenesis in pancreatic cancer is worthy of further study, offering new hope to those affected by this difficult disease.