Efforts in this activity, have focused on the development of new agents and new treatment combinations for recurrent ovarian cancer, and newly diagnosed ovarian cancer. In newly diagnosed ovarian cancer, we continue with our three-drug regimen of paclitaxel, cisplatin, and cytoxan with G-CSF support. Follow-up data show continued high levels of pathologic complete response, and disease free survival. In recurrent disease, we now conduct three phase II studies. MGI-114 is a novel DNA damaging agent that is active in platinum-resistant cell lines. Clinical data to date shows substantial activity in patients with platinum-resistant tumors. Active accrual continues. 9-AC is a topoisomerase I inhibitor, and our phase II study is reaching its accrual limit. We show a level of activity comparable with topotecan, but with a lessened toxicity profile. CAI is an anti-angiogenesis agent with good ability to induce disease stabilization, which we are using primarily in the setting of less aggressive disease. A phase I study is about to begin accrual with SU5416 and carboplatin. SU5416 is an anti- VEGF agent. VEGF expression is directly linked to poor survival in ovarian cancer. By direct inhibition of VEGF, we anticipate that there will be activity in this disease. In addition, SU5416 appears to have properties that may result in inhibition of platinum-DNA adduct repair. The trial is designed to take advantage of possible synergism between these two agents. Preclinically, efforts are being made to develop ways to reverse the platinum-resistant phenotype. Two approachs that appear to have particular promise at this point include; dominant negative constructs to the transcription factor AP1, and the use of proteasome inhibitors. - ovarian cancer, pharmacology, platinum compounds, angiogenesis, - Human Subjects
