Overcoming drug resistance in ovarian carcinoma.

Advanced epithelial ovarian carcinoma is treated with cytoreductive surgery and combination chemotherapy with a platinum compound and paclitaxel. Despite this treatment strategy, most women eventually relapse and die of resistant disease. Preclinical studies have shown that alterations in drug accumulation, drug metabolism, DNA repair, cellular targets and/or cell survival pathways may cause this resistance. Clinical studies have employed modulators of resistance in combination with chemotherapy as a means to overcome drug resistance. The most extensively studied modulators, buthionine sulfoximine and valspodar, are involved in reversing resistance caused by glutathione and P-glycoprotein, respectively. A phase III study comparing paclitaxel and carboplatin with and without valspodar is ongoing. However, other approaches to overcoming drug resistance are necessary for the effective treatment of women with this disease.