Ovarian Cancer: Combination Therapy Using Decitabine 'Effective'

Women with recurrent ovarian cancer showed clinical benefit when treated with a drug called decitabine before undergoing chemotherapy and a cancer vaccine. This is according to a new study published in the journal Cancer Immunology Research.

The research team, led by Dr. Kunle Odunsi of the Roswell Park Cancer Institute in Buffalo, NY, say their findings suggest that this combination of "chemoimmunotherapy" could give patients with ovarian cancer a new treatment option for the disease. The investigators say their main focus in the study was on a tumor antigen called NY-ESO-1. They explain that in order for a cancer patient's immune system to distinguish and attack a tumor, there must be high levels of a foreign protein in their healthy cells. These proteins are known as tumor antigens, and the researchers say these antigens are good targets for anticancer vaccines. Dr. Odunsi says the team focused on NY-ESO-1 for the development of cancer immunotherapy because it is "one of the few tumor antigens that have restricted expression in normal tissues but become aberrantly expressed in epithelial ovarian cancers and other solid tumors." But he says that NY-ESO-1 is not "uniformly expressed" by epithelial ovarian cancers. Therefore, they set out to force expression of the antigen on ovarian cancer cells so the immune system could recognize and attack the cells.

Set Combination of Drugs Administered. The team recruited 12 women with epithelial ovarian cancer who had been unresponsive to multiple chemotherapy treatments. All women were estimated to have a 3-month progression-free survival time. Since NY-ESO-1 expression is regulated by a process called DNA methylation, Dr. Odunsi explains that the team tested a demethylating drug called decitabine on the women, with the hypothesis that the drug would reprogram NY-ESO-1 and therefore trigger "vaccine-induced immunity." All women were given decitabine on the first day of the study. They were randomized to receive either a low, middle or high dose of the drug. The investigators note that preclinical studies had shown that decitabine was most effective when given to patients prior to chemotherapy. Doxorubicin - a chemotherapy drug - was given to the women on day 8, while the cancer vaccine was given to the women on day 15. The vaccine was made up of the NY-ESO-1 protein, montanide - an immune response booster - and a protein known as granulocyte macrophage colony-stimulating factor (GM-CSF). Up to 60% of patients 'showed clinical benefit' At the end of the study, 10 of the patients were able to be assessed for clinical response.

Of these, five had stable ovarian cancer for up to 7.8 months, while one patient demonstrated a partial response and experienced disease remission for 5.8 months. Clinical benefit was seen in all patients who received low and middle doses of decitabine, and of patients who received high doses of the drug, one-third showed clinical benefit. Dr. Odunsi says their findings suggest that lower doses of decitabine are linked to improved clinical response when administered using this set regime. Dr. Odunsi adds: "Although clinical results were not a focus of this phase I trial, we saw evidence of clinical benefit in up to 60% of the patients with chemotherapy-resistant tumors. The combination of a demethylating agent, chemotherapy, and cancer vaccine may have enabled this remarkable effect." Furthermore, he notes that their results revealed that this combination therapy triggered "antigen spreading." The team found that they induced immune responses against three other antigens, even though they only immunized against NY-ESO-1.

Based on their findings, Dr. Odunsi says the team believes patients with ovarian cancer should "actively seek" similar combination therapies. "Even though the majority of these types of therapies are experimental at this point, there is enough scientific and clinical evidence to indicate that they are likely to be beneficial," he adds. The research team says that are in the process of planning a phase II trial, in which they hope to determine whether the combination treatment detailed in this study is able to prolong progression-free survival for patients with ovarian cancer. Additionally, recent reports on a study suggest that frankincense may be effective against ovarian cancer cells.