Combined oral cyclophosphamide and bevacizumab in heavily pre-treated ovarian cancer.

Introduction: Metronomic chemotherapy combined with bevacizumab has proved to be effective in various tumour types. The aim of this study is to review our experience in recurrent ovarian carcinomas treated with low-dose cyclophosphamide and bevacizumab.

Materials And Methods: Retrospective analysis of pre-treated ovarian cancer patients, i.e., > or =2 previous chemotherapy regimens who received treatment with oral cyclophosphamide 50 mg/day and bevacizumab 10 mg/kg IV every two weeks. Patients with a performance status 0-2 were included. The endpoints were response rates, progressionfree disease and safety profile.

Results: Nine patients with advanced, measurable ovarian cancer were included. Of these, 8 were platinum-resistant and had received prior regimens with gemcitabine (88%), topotecan (77%) and liposomal doxorubicin (66%). There was a mean of 5 previous lines of chemotherapy, range 2-7. Applying RECIST criteria, the efficacy data were as follows: objective response (OR) 44%; 4/9 (CR 2/9 and PR 2/9), SD 2/9 and DP 3/9. At 6 months, 33% of patients were progression free. Response lasted for 12.5 months in three patients treated for 12 months; a further two patients who were re-treated achieved complete response. Mean time to progression was 5.5 months (95% CI 4.5-5.5). No severe adverse effects were reported. Only one patient had to delay several cycles due to G3 haematuria. Other toxicities observed include G3 abdominal pain (1 case); G2 mucositis and G2 dyspnoea in one patient.

Conclusions: Combined bevacizumab and metronomic oral cyclophosphamide is a safe and effective regimen for heavily pre-treated ovarian cancer patients. Further research is needed on predictive factors to screen for those patients who will benefit from anti-angiogenic therapy.