PROMISING NEW THERAPIES IN THE TREATMENT OF ADVANCED OVARIAN-CANCER

Advanced stage ovarian cancer is the most lethal gynecologic cancer. D espite initial response rates of 60-80% with platinum-based chemothera py, more than 75% of women with this malignancy die of complications a ssociated with this disease. There is a pressing need to find new chem otherapeutic agents for patients with advanced ovarian cancer. Phase I I studies have identified paclitaxel as the most active drug in ovaria n cancer since the introduction of cisplatin in the 1970s. Phase III s tudies will define the role of paclitaxel as initial therapy. Camptoth ecins (topotecan, CPT-11, 9-amino-camptothecin) inhibit topoisomerase I. CPT-11 and topotecan have shown activity in Phase II trials. Gemcit abine, a pyrimidine antimetabolite, has shown activity in Phase II tri als. Other promising drugs (docetaxel, treosulfan) are under investiga tion. Modulation of drug resistance is being explored in Phase I/II st udies. Clinical trials have been initiated with buthionine-sulfoximine , an inhibitor of glutathione biosynthesis, which decreases the abilit y of resistant cells to inactivate platinum compounds and alkylating a gents. Cyclosporin has been shown to increase cisplatin cytotoxicity. Phase I trials have demonstrated the feasibility of combining cyclospo rin and cisplatin. Phase II trials of cyclosporin analogs (PSC 833) an d paclitaxel in refractory ovarian cancer are ongoing. Promising leads in drug development should provide new therapies for patients with ov arian cancer. Further research in the modulation of drug resistance ma y identify new mechanisms or strategies with which to prevent the emer gence of drug resistance.