SuperGen Inc and Cancer Research UK announced the initiation of a Phase I/II clinical study of Dacogen (decitabine), in combination with carboplatin, in cancer patients with advanced solid tumors.

The study, with an anticipated enrollment of between 20 and 40 patients at the Beatson Oncology Centre in Glasgow and the Royal Marsden Hospital in London, will examine the toxicity, pharmacokinetics and pharmacodynamics of intravenous Dacogen, in combination with standard doses of carboplatin, administered to patients with advanced solid tumors. Once the optimal dose level of both agents has been identified, it is anticipated that the efficacy of the regimen will be tested in an expanded cohort of patients.

Dacogen is an inhibitor of DNA methyltransferase, which in preclinical studies has demonstrated the ability to sensitize drug resistant tumor cells to conventional cytotoxic agents, such as cisplatin and carboplatin. The work is based upon in-vivo data published by Dr. Robert Brown from the Beatson Cancer Institute in the United Kingdom using multiple combinations of chemotherapies with Dacogen.

The primary mechanism of action for Dacogen in cancer is thought to be the correction of aberrant DNA methylation, a major mechanism for regulating gene expression and reversing resistance to chemotherapy treatment. When suppressor genes are silenced, cell division becomes unregulated, and may be associated with the formation of cancer cells. Silencing of suppressor genes via hypermethylation is an early key event in the development of cancer.

Earlier this year, SuperGen announced that patient enrollment has been completed in an open-label, randomized Phase III clinical study of Dacogen in the treatment of patients with advanced myelodysplastic syndrome (MDS). One hundred seventy patients have been enrolled at 22 clinical sites around the United States, with half receiving Dacogen plus "standard of care" and the other half receiving the current "standard of care" therapy only.

Cancer Research UK's mission is to conquer cancer through world-class research. It is the largest volunteer-supported cancer research organization in the world, with a dedicated team of 3,000 scientists and an annual scientific spend of more than 176 million pounds sterling, raised almost entirely through public donations.