SuperGen Inc announced that clinical studies suggest the anticancer drug decitabine is effective in elderly patients with high-risk myelodysplastic syndrome (MDS).

Comprehensive data on 169 patients from a series of Phase II clinical studies is being presented by principal investigator Dr. P.W. Wijermans of Leyenburg Hospital in The Hague, Netherlands. An overall response rate of 68 per cent was observed (complete responses, partial responses and haematological improvement comprised 49 per cent, and stable disease 19 per cent). A significant increase in platelets was also observed in 42 per cent of the patients after one cycle of therapy, and 63 percent after two cycles. The median survival was 15 months, which is a two-fold increase over previously published studies, and the two-year survival rate was 34 per cent.

"MDS is a rare disease with an inevitably fatal outcome. Treatment is cumbersome, especially in elderly patients," said Dr. Wijermans. "We conclude from these Phase II data that decitabine is a rather mild drug that can be used even in old patients with high risk MDS."

"Today's findings bolster our belief that decitabine is a potential treatment for a broad cross section of persons with MDS that has no approved treatment," said Dr. Joseph Rubinfeld, chairman and chief executive officer of SuperGen. "We are in the last-stages of patient enrollment for our multicenter Phase III pivotal study of decitabine as a treatment for MDS. Patient enrollment should be complete by the end of January 2003.

"Throughout the duration of the ASH annual meeting, 14 presentations will be made on decitabine, either detailing clinical results in a variety of conditions or further validating the drug's novel mechanism of action, which is the reversal of DNA hypermethylation," added Dr. Rubinfeld. "We have always believed that decitabine is a 'franchise compound', and could be used to treat a number of hematological malignancies and solid tumors. From the depth and breath of the published data, it is clear that this unique anticancer agent is capturing the attention of the oncology community."

MDS is a disorder that is a pre-cursor to leukemia and is often fatal. According to the American Cancer Society, about 14,000 new cases of MDS are diagnosed in the United States each year, and the number of new cases diagnosed each year is steadily increasing. The average life expectancy for patients diagnosed with MDS is anywhere between 6 months and 5 years, depending on the severity of the disease.

The primary mechanism of action for decitabine is thought to be the correction of DNA hypermethylation, a major mechanism for regulating gene expression. In some cancer cells a condition known as 'hypermethylation' blocks the activity of several 'tumor suppressor genes' that regulate cell division and differentiation to prevent unregulated malignant transformation. When suppressor genes are silenced, cell division becomes unregulated, often leading to the formation of cancer cells. Decitabine's unique mechanism of action - inhibition of DNA hypermethylation - specifically targets the series of events that lead to the formation of malignant cells. Silencing suppressor genes via hypermethylation is an early key event in the development of cancer.