An experimental drug that attacks cancer in an entirely new way has shown promise in treating advanced melanoma, delaying progression of the disease and prolonging the lives of patients.
New research presented September 26 at the European Cancer Conference in Barcelona found that giving the new drug in addition to chemotherapy more than doubled the amount of time patients survived without progression of their cancer.
The study, according to Dr Anthony Williams, vice president of clinical research at Synta Pharmaceuticals Corp. in Lexington, Massachusetts, USA, included 81 patients with metastatic melanoma. Of those, 28 received treatment with the chemotherapy drug paclitaxel alone and 53 received paclitaxel plus the new drug, STA-4783.
“The median progression free survival was 1.8 months in the group who got chemotherapy alone, but 3.7 months in the group who got the combination,” Williams said. “This doubling in progression free survival is impressive for this cancer, and the result was achieved without substantial additional toxicity.”
He added: “Progression-free survival was linked to improvements in overall survival. Patients on the experimental combination survived on average for 12 months after being diagnosed, while those getting only paclitaxel survived on average 7.8 months. This is the first time an improvement in survival has been seen in a randomised, double-blind, multi-centre controlled trial for metastatic melanoma.”
The drug is the first in a new class called oxidative stress inducers. It works by increasing the amount of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide, in cells. When the level exceeds the antioxidant capacity of cells, the cells are in a state of oxidative stress. All cells have some low level of ROS, but cancer cells naturally operate with a higher level of ROS and oxidative stress relative to normal cells. However, too much oxidative stress for too long results in cell death. STA-4783 kills only tumour cells because the additional stress introduced pushes cancer cells, but not healthy cells, over the critical threshold. Melanoma is one of several cancer types that are known to operate at a higher level of oxidative stress.
The concept of cancer cells operating at a higher level of oxidative stress than normal cells has been around for many years. However, it is only recently becoming a greater focus of attention in the oncology field.
Metastatic melanoma, where the skin cancer has spread to other parts of the body, is difficult to treat. Current therapies either have limited power or are highly toxic. The average survival of patients diagnosed with advanced melanoma is about six months.
The study also indicated that STA-4783 might boost the efficiency of chemotherapy drugs that induce cell death, or apoptosis, because it appears to lower the hurdle for activating that process, Williams said.
“These results are encouraging not only because of the findings in themselves but also because there are so few treatment options for patients. We believe STA-4783 has the potential to improve survival with a manageable side effect profile,” he said.
“We also believe there is nothing unique about metastatic melanoma and that oxidative stress has the potential to be an entirely new class of cancer treatment that could have applications in other types of cancer,” Williams added.
A larger study of STA-4783 in melanoma patients across Europe is now under way to further investigate the drug’s potential. Synta, the drug’s developer, funded the study presented at ECCO.
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