Bevacizumab and oral metronomic cyclophosphamide in platinum-resistant ovarian cancer

of the affected patients. Despite improvements in treatments, the 5-year survival rate remains poor. Over 70% of patients with advanced ovarian cancer will relapse and despite a good chance of remission from further chemotherapy, patients eventually become resistant to cytotoxic agents. Efficient alternatives to chemotherapy are thus urgently needed. Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that targets vascular endothelial growth factor-A. As a single-agent drug, it has shown response rates of 16%-21% in the treatment of recurrent ovarian cancer. Four phase III randomized trials have been reported evaluating the addition of bevacizumab to standard chemotherapy as front-line treatment or in the recurrent setting of advanced ovarian cancer [1-4]. All these trials showed a statistically significant improvement in progression-free survival (PFS), although no improvement in overall survival has yet been reported, except in some subset of patients. The main adverse event is hyper-tension. Other serious, but uncommon adverse events include gastrointestinal perforation as well as renal or vascular toxicity. Overall, bevacizumab is the first biological therapy to have shown efficacy in ovarian cancer and to obtain approval in certain countries. In this issue, Barber et al. [5] reported 42.4% of an impressive overall response rate, including 10.6% of complete response rate in 66 patients with heavily pre-treated recurrent platinum-resistant ovarian cancer when they were offered a combination of bevacizumab and oral metronomic cyclophosphamide (OMC). Despite this remarkable tumor shrinkage activity, the median PFS remained relatively short, between 3 months for the whole population and 5 months for the responders. However, this modest duration of disease control has to be put in the context of women who had received previously a median of 6.5 lines of chemotherapy. The results reported in this study are in line with those previously reported in similar retrospective studies of heavily pre-treated ovarian cancer patients treated with bevacizumab and OMC with a 40%-53% of response rate and 3.9-5.5 months of PFS. Adverse events were those expected with bevaci-zumab treatment and only one patient suffered from bowel perforation. Unfortunately, because it is a retrospective study, patient-reported outcomes such as quality of life and control of patient symptoms, which are considered as important objectives of treatment in recurrent platinum-resistant ovarian cancer, were not captured. The substantial activity of the bevacizumab-OMC combination observed in this series of patients addresses the question of bevacizumab synergy with chemotherapy in general, and OMC in particular, in the recurrent ovarian cancer setting. …