Sequential bevacizumab and oral cyclophosphamide for recurrent ovarian cancer.

OBJECTIVE: Test the safety and efficacy of sequentially blocking angiogenesis by adding oral cyclophosphamide to bevacizumab following cancer progression on bevacizumab in patients with recurrent ovarian cancer. METHODS: Eligibility included ≤ 2 lines of treatment for recurrence and measurable cancer by RECIST 1.0. Patients received bevacizumab (15 mg/kg every 3 weeks IV) and upon RECIST progression, oral cyclophosphamide (50mg orally daily) was added. Objectives included safety, toxicities, 3- and 6-month PFS rates, response rate, PFS, and OS. RESULTS: 20 patients were enrolled. Overall response rate was 10%, and 65% of patients had confirmed stable disease (SD). Thirteen of 20 patients received oral cyclophosphamide added to bevacizumab upon bevacizumab progression. Of these 13 patients, 1 patient subsequently achieved a PR (this patient had SD as best response during bevacizumab) and 3 patients had a confirmed SD. For all patients, median PFS was 8.41 months, 6 month PFS rate was 65%, duration of response (DOR) was 7.3 months, and median OS was 22.72 months. Median DOR for patients receiving both bevacizumab and cyclophosphamide was 8.4 months. Most toxicities were grades 1 and 2 and manageable. Grades 3 and grade 4 toxicities included 1 myocardial infarction, 1 gastrointestinal perforation (GIP), and 12/20 patients (60%) developed grade 3 HTN. CONCLUSIONS: Addition of oral cyclophosphamide to bevacizumab at the time of cancer progression on bevacizumab appears to have continued anti-cancer effects in a subgroup of patients and appears to be safe. Randomized trials testing combination versus sequential anti-angiogenic therapy for recurrent ovarian cancer are warranted.