Treatment approaches are being developed that are directed against two different disease categories. The first is the treatment of advanced stage epithelial disease of histological grades 1, 2, and 3 using cisplatin, paclitaxel (Taxol) and cytoxan. The second is the treatment of poor prognosis patients who had advanced stage disease of borderline histology. We have recently completed a phase I study of the three drug combination of cisplatin, paclitaxel and cytoxan. The dosing combination to be used in a phase II study that will get underway shortly is cisplatin 75mg/m2/cycle, paclitaxel 250mg/m2/cycle, and cytoxan 750mg/m2/cycle, with G-CSF support. The results of the phase I study are being prepared for publication at this time. Briefly, this cohort was heavily weighted towards bulky disease at the initiation of therapy, as well as heavily weighted towards poorly differentiated disease. Even so, the objective response rate exceeds 80%; the pathologic response rate is better than what has been reported with any two drug combination; and durability of response has yet to be fully assessed. Patients with borderline histology disease are generally characterized by a slowly growing malignancy, associated with prolonged survival. However, subsets of patients have been identified (based on clinical criteria) that will have survival measured in months to several years (i.e., a severely shortened survival as compared to most patients). This clinical observation, along with recently reported laboratory data, suggest that """"""""borderline histology"""""""" disease may be a transition state between benign ovarian tumor growths, and frankly invasive malignant disease. A study is being initiated to treat patients who have the clinical criteria of poor prognosis borderline histology, with aggressive chemotherapy. These patients will also be followed with measures of molecular markers of tumor invasiveness, as well as selected oncogenes.
