Ovarian cancer is diagnosed in 20,000 women annually in the United States and is the fourth most common cause of cancer deaths in this population. Such poor survival figures are related to the advanced degree of disease at presentation in addition to the inadequate cytotoxic therapies that exist for the treatment of the disease. Cisplatin and its analogues used alone or in conjunction with either alkylating agents or pacilitaxel remain the most important classes of agents for treating patients with advanced disease. However even with the advent of newer classes of agents such as the taxanes the prognosis for patients with ovarian cancer remains poor with 5 year survival rates of 25 and 5% for patients with Stage III or IV disease, respectively. The inability to cure ovarian cancer is almost certainly due to intrinsic and acquired resistance to drug therapy and attempts to overcome this resistance have not resulted in significant alterations in response for patients with platinum refractory disease. Broystatin-possesses anti-tumor activity in vitro and in vivo against a variety of tumors including leukemia, melanoma, and lung cancer. In vitro, bryostatin-1 induced the differentiation of various human B-cell NHL cell lines and of chronic B-cell leukemia cell lines. Bryostatin-1 induced apoptosis in a diffuse large cell lymphoma cell line in vitro and exposure of these cells to vincristine following bryostatin-1 resulted in increased apoptosis compared to cells exposed to either agent alone. Of interest, bryostatin-1, like other agents that inhibit protein kinase C activity, has been reported to potentiate the in vitro apoptosis induced by a variety of cytotoxic agents in a number of tumor cell lines. Brostatin-1 has undergone Phase I testing employing three different schedules of administration. Two Phase I clinical trials of bryostatin administered as a one hour infusion either every two weeks or weekly for three of every four weeks were reported. The main dose-limiting toxicities were cellulitis and phlebitis at the site of infusion, and myalgia. When bryostatin-1 was administered intravenously over one hour for three of every four weeks, the recommended Phase II doses was 25ug/m2 and partial responses were reported in two patients with melanoma. This regimen has now entered Phase clinical trials in patients with lymphoma, hypernephroma, and melanoma.

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