Interim report of a phase II clinical trial of bevacizumab (Bev) and low dose metronomic oral cyclophosphamide (mCTX) in recurrent ovarian (OC) and primary peritoneal carcinoma: A California Cancer Consortium Trial

Abstract

5000 Background: Bev is a recombinant humanized anti-VEGF monoclonal antibody that inhibits the growth of a number of human cancers, including ovarian cancer. Low dose chronic chemotherapy (metronomic chemotherapy) inhibits angiogenesis. In preclinical models enhanced antitumor activity has been observed with the combination of anti-VEGF antibodies and metronomic chemotherapy. Methods: We developed a 2-stage phase II study to evaluate the activity and toxicity profile of the combination of Bev and mCTX in recurrent OC and to explore serologic markers of angiogenesis and genetic polymorphisms as potential surrogate markers of response and/or toxicity. Bev 10 mg/m2 i.v. was administered on days 1, 8 and 15 and then every 2 weeks with CTX 50 mg po qd. Patients were required to have uni-dimensionally measurable disease, recurrence after platinum and paclitaxel chemotherapy, 0–2 chemotherapy regimens for recurrent disease and performance status 0–2. Results: 29 patients have been enrolled and are evaluable for response. Median age 57 (39–83). Prior chemotherapy included: platinum and paclitaxel (100%), liposomal doxorubicin (31%), topotecan (31%). Grade 3–4 toxicities include: pain (6), hypertension (3), hyponatremia (3), urinary (2), fatigue (2), lymphopenia (2), gastrointestinal obstruction (2), and increased transaminases, thrombosis, prolonged PTT, CNS ischemia, hyperglycemia, hypomagnesemia, edema, hot flashes, pulmonary and arthritis (1 each). No treatment related deaths. Median number of courses 4 (range 2–9). Best response: 6 PR (21%), 17 SD (59%) and 6 PD (21%). Median PFS 5.8 months (95% CI 3.8–8.1), PFS at 6 months 47% (± 11%). Conclusions: Based on the encouraging response rate and 6 month PFS the second stage of accrual was opened. Correlation with serologic markers and genetic polymorphisms is ongoing. The combination of Bev and mCTX shows encouraging activity in recurrent ovarian cancer. Supported in part by NCI N01 CM17101 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech