Ovarian Trial Welcome to Advantagene

Advantagene also has safety data from a completed Phase I study in ovarian cancer with positive indications. However, due to limited resources, the Company is not currently pursuing this indication.

Ovarian cancer is the leading cause of death from gynecological cancer. Mortality from ovarian cancer accounts for 6% of cancer deaths in females, and approximately 50% of gynecological malignancies. In the United States there are approximately 19,000 new cases and 12,000 deaths from ovarian cancer each year. On a worldwide basis, the total number of cases has been estimated to be approximately 140,000, thus representing over 4% of all cancers in women and the seventh leading site of incidence.

Ovarian cancer is staged into four categories according to the Federation International de Group Oncologies (FIGO): Stage I, growth limited to ovaries; Stage II, growth involving one or more ovaries with pelvic extension; Stage III, tumor extending outside the pelvis and/or retroperitoneal or inguinal node involvement; and Stage IV, distant metastasis outside the peritoneal cavity. The first three stages can be divided into three substages of more progressive disease (a,b,c).

Ovarian cancer is often asymptomatic until it has disseminated. In 75% of patients with ovarian cancer, the tumor has spread beyond the ovary at the time of clinical diagnosis, resulting in an overall 5-year survival of 28% to 35%. Patient survival can be predicted based on the stage of the disease at diagnosis. Higher stage disease correlates with a worse prognosis. Treatment of ovarian cancer is based on the stage of the disease. Higher stages of disease are treated more aggressively. Stage I disease can be treated with surgery or surgery and chemotherapy. Patients with Stage II, III and IV disease initially undergo aggressive surgical tumor debulking before receiving chemotherapy. Following the initial surgery, patients may alternatively be treated with intraperitoneal chemotherapy with liquid drugs or by intravenous chemotherapy. Therefore, the technology for the installation into the peritoneal cavity for treatment of ovarian cancer is well established.

In Advantagene's ovarian cancer Phase I trial, ten patients with recurrent stage IIIc ovarian cancer underwent secondary debulking followed by intraperitoneal administration of AdV-tk, subsequent IV acyclovir or oral valacyclovir and concurrent therapy with topotecan (Hasenburg et al, 2002). Five patients received second-look surgery four weeks after gene therapy administration, two of which were found to be tumor-free. Median overall survival was 18.5 months with three patients still alive 30 months after gene therapy. These results are encouraging in comparison to survival observed in similar patients not receiving gene therapy, although efficacy conclusions cannot be made from this small study.