Achievements and unmet needs in the management of advanced ovarian cancer

Ovarian cancer is the second most common gynaecological malignancy, and represents the leading cause of gynecologic cancer-related death in Europe and United States. The majority of the cases are in fact diagnosed in advanced stage, with limited chance to be cured. Optimal management of advanced ovarian cancer includes histopathological diagnosis, accurate surgical staging, debulking surgery and platinum-based chemotherapy. The combination of carboplatin and paclitaxel is commonly recognised as the standard regimen because of tolerability and activity. Intraperitoneal chemotherapy provides superior efficacy results, but its use is still controversial because of poor tolerability and compliance. Unfortunately, despite its chemosensitivity, the majority of ovarian cancer patients, including those who achieve a complete response to first-line chemotherapy, will relapse and eventually die. Among the strategies to improve patient outcome, maintenance therapy has failed to show a consistent benefit across clinical trials. Salvage second-line therapy is generally based on rechallenge with platinum in patients with platinum sensitive disease. Patients with platinum resistant/refractory might benefit from liposomal doxorubicin or topotecan. Other active cytotoxics include docetaxel, gemcitabine, etoposide and vinorelbine as well as epothilone derivatives such as patupilone which is still in development. Among targeted agents, the antiangiogenic agent bevacizumab seems extremely promising and is actively investigated in combination with first-line chemotherapy. More recently, interesting results have been obtained with the inhibitors of poly-ADP-ribose polymerase (PARP) in patients with BRCA-mutated tumors.