The current standard of treatment for patients with advanced ovarian cancer has been established in light of the results from various clinical trials. After debulking surgery, a combination of carboplatin and paclitaxel is considered to be the best treatment option in terms of survival and quality of life. However, since most patients on this chemotherapy modality will experience relapse, several studies have explored, and continue to do so, various modifications and alternatives to standard therapy in order to attain improved efficacy. Various modifications of dose, schedule, or route of standard regimens have shown no benefit, apart from intraperitoneal therapy, which has produced mixed results and would benefit from a definitive trial. Studies of maintenance/consolidation therapy have been mainly negative, although a small number of trials have produced enough positive data to prompt two new studies powered to detect survival benefits. Various phase II trials have investigated “targeted therapies,” but until now no positive results have been recorded. Translational studies are needed to identify patients who will benefit from such specific treatment strategies. The current most evaluated modification of standard therapy is the addition of a third non–cross-resistant drug to carboplatin and paclitaxel. Data for the addition of anthracyclines have either been negative (epirubicin) or not yet analyzed (pegylated liposomal doxorubicin), while evaluable data are shortly expected for the addition of topotecan. Data on the addition of gemcitabine are eagerly awaited from two phase III trials.

This review displays the AGO Ovarian Cancer Study Group approach towards evaluation of improvement options in first-line therapy of advanced ovarian cancer. Prospectively randomized phase III trials evaluating the addition of newer drugs to standards carboplatin-paclitaxol (TC) as well as pilot trials evaluating new treatment modalities like anti-idiotype CA 125 antibodies or epidermal growth factor receptor (EGFR) modulation are presented.