Anticancer agent - Virulizin
Cancer remains a big killer, despite the major advances that have been made in cancer therapies in recent years. The mainstays of treatment are radiotherapy, surgery and cytotoxic drugs, plus hormone modulators in hormone refractory cancers. However, side-effects of cytotoxic drugs can be treatment limiting, so improved regimes and approaches are required, as well as solutions for cancers that are currently very difficult to treat.
A different approach to cancer treatment is immunotherapy. Rather than directly affecting the cancer cells, it relies on the drug's ability to activate the body's immune system so that it recognises and then eliminates the cancer cells. Solid tumours have antigens that the immune system can recognise, particularly the macrophage white blood cells. When these are activated, they are thought to enhance the immune system's rejection of tumours by the production of cytokines that either kill the tumour cells directly, or stimulate the antitumour activity of other cell types.
Virulizin is a new product being developed by Lorus Therapeutics that acts as a macrophage enhancer. It is an aqueous solution containing 5% w/v solids, most of which are inorganic salts and the rest organic compounds. It is obtained from bovine bile by a standardised process involving solvent extraction and heat hydrolysis. In vitro studies showed that it can stimulate blood monocytes, peritoneal macrophages and alveolar macrophages. It also stimulates the release of tumour necrosis factor by tumour cells in vitro.
In a Phase II trial in patients with pancreatic cancer, 22 subjects were given 0.11 ml/kg of Virulizin three times a week for the first week, then twice a week until disease progression occurred.1 Although there was no evidence of tumour regression, six had their diseases stabilised for more than three months, and two for at least 15 months.
An investigation in mouse models bearing human tumours has proved promising.2 Three different pancreatic tumours and two forms of melanoma were studied, and Virulizin showed a high level of antitumour activity. It was also tested in combination with the anticancer agents Gemcitabine and 5-fluorouracil against the pancreatic tumours, and with decarbazime against metastatic melanomas. It significantly enhanced their antitumour activity compared with the action of the conventional drugs alone.
The product has been awarded orphan drug status by the FDA, and is currently undergoing Phase III trials in combination with gemcitabine for the treatment of pancreatic cancer.
1. E. Warner et al. Clin. Invest. Med. 1994, 17, 37
2. N. Feng et al. Cancer Chemother. Pharmacol. 2003, 51, 247