Scientists seeking treatments for a deadly types of skin cancer say an existing arthritis drug slows the growth of melanomas and could be combined with a drug under development by Plexxikon and Swiss drug maker Roche.
In laboratory studies using mice and human cancer cells the researchers found that leflunomide, a generic drug commonly used to treat rheumatoid arthritis, also inhibits the growth of melanomas.
If further trials prove successful - both for leflunomide alone and in combination with Roche and Plexxikon's promising new melanoma drug PLX4032 - patients could have access to new treatments in three to five years, they said.
Japanese drug maker Daiichi Sankyo bought Plexxikon for $805 million in March.
"This is a really exciting discovery - making use of an existing drug specifically to target melanoma," said Grant Wheeler of Britain's University of East Anglia, who worked on the study with scientists from the Children's Hospital Boston.
Melanomas are tumours of the pigment cells in skin. It is the most aggressive form of skin cancer and affects around 160,000 people worldwide each year.
If caught early, surgery can be used to remove the tumour, but if the cancer returns and spreads there are virtually no good alternative treatments, and conventional chemotherapy typically works in only around 10 to 20% of these cases.
Series of experiments
The British and US scientists began their series of experiments by looking at the effects of various chemical compounds on pigments in frogs and zebra fish. This screening process led them to leflunomide, which they then tested on tumours in mice engrafted with human melanoma cells.
Leflunomide was sold under the brand name Arava by Sanofi-Aventis and is now sold generically by drug makers such as Teva Pharmaceutical Industries.
After seeing that the drug slowed the growth of these tumours, the group combined it with Roche and Plexxikon's drug - a so-called BRAF inhibitor, currently in late stage trials.
"We thought combining that drug, which targets a specific oncogenic mutation, with leflunomide, which changes the cell's lineage, could have a beneficial effect," said Leonard Zon, one of the research team leaders from Children's Hospital Boston.
Their results showed that it did. Compared with each drug alone, the combination led to a marked decrease in melanoma, the researchers said, and even with low doses of each drug the tumours disappeared completely in 40% of the mice.
The researchers said the results from these studies, which were published online in the journal Nature, mean human trials could start within the next 6 months, since the safety of both drugs has already been established.
"Deaths from melanoma skin cancer are increasing and there's a desperate need for new, more effective treatments," Wheeler said. "If this does what we think it will, and we find patients are responding to it in the trials, it could be used in patients in three to five years."
Bristol-Myers Squibb also has a new experimental melanoma drug called ipilimumab in late stage trials. Preliminary data released this week showed it extended survival of previously untreated patients with advanced forms of the disease.
Preventing skin cancer