Continuing therapy beyond adjuvant chemotherapy to optimise cure in advanced ovarian cancer: A dream coming true?

Abstract

The GOG111 and OV-10 were pivotal studies published in 1996 and 2000 respectively which established paclitaxel I cisplatin as standard postoperative adjuvant chemotherapy for advanced epithelial ovarian cancers. A second major breakthrough in the ensuing past decade has yet to be witnessed. Carboplatin has been proven to confer similar efficacy when combined with paclitaxel with much less neurotoxicity in the GOG158 and AGO studies that were reported in 2003, and have since been adopted as standard clinical practice. Replacing paclitaxel with docetaxel, delivery of cisplatin intraperitoneally, or adding a third agent to form triplets have not produced impressive improvements. Moreover, they were not widely accepted due to technical difficulties and unacceptable toxicities. For stage III/IV cancers, despite a high clinical response rate of 70 to 80% and a pathological complete response rate of ∼30% after 6 to 8 cycles of paclitaxel I carboplatin following primary cytoreductive surgery, the median overall survival remains relatively low at ∼26 months for those with bulky residuum, and ∼60 months for those with optimal cytoreduction, translating into a 5-year overall survival of ∼30 to 40%. The median progression-free survival remains at around 16 months only for patients with stage IV and stage III disease after suboptimal cytoreduction, and at 24 months only even for those with stage III after optimal cytoreduction. The resulting low 5-year progression-free survival of approximately 20% indicated continuous disease relapses or progression following postoperative chemotherapy and hence the concept of effective consolidation or maintenance therapy appeared attractive. Over the years, studies involving sequential I consolidation standard-dose oral or intravenous 'second-line' chemotherapy, intraperitoneal chemotherapy, high-dose chemotherapy with stem cell transplantation, external beam radiotherapy or intraperitoneal radiotherapy with radioactive phosphorus or radioactive monoclonal antibody have largely failed to improve outcomes. More recently, results of randomised studies testing biological therapies such as interferon, CA125-specific monoclonal antibody, multi-targeting agents and anti-angiogenesis targeted therapy have also been reported, but yielded variable results. Early results from 2 recent randomised studies suggest progression-free survival benefit by adding bevacizumab concurrently with, and then as prolonged maintenance therapy following postoperative adjuvant paclitaxel / carboplatin chemotherapy. © 2010 Hong Kong College of Radiologists.