Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refractory epithelial ovarian cancer

Abstract

Objectives.: Bevacizumab (BEV) is a humanized monoclonal antibody against vascular endothelial growth factor. We reviewed our experience with BEV in patients with recurrent advanced epithelial ovarian cancer who had failed multiple prior chemotherapeutic regimens. Methods.: Thirty-two patients not participating in an ongoing clinical trial were treated with BEV (15 mg/kg every 3 weeks IV). Demographic and clinicopathologic data, clinical outcomes, and adverse events were extracted from patient charts. RECIST and CA-125 Rustin criteria were retrospectively applied to evaluate response and progression. Median progression-free survival (PFS) and overall survival (OS) were determined using Kaplan-Meier methods. Adverse events were retrospectively categorized using the common terminology criteria for adverse events version 3. Results.: The median patient age was 57 years (range 35-80) with 84% being Caucasian and 50% having a GOG performance status of 2. FIGO stages included 80% stage III and 10% stage IV. The tumors were mostly grades 2 (29%) and 3 (64%) and serous histological subtype (69%). All patients had failed multiple prior cytotoxic chemotherapies (median of 5 (range 2-10)) prior to BEV. The median duration of follow-up was 4.8 months (range 0.4-16.3). Twenty-three patients were treated with BEV alone, 2 received BEV with another chemotherapy regimen (5-FU/lecovorin plus oxaliplatin, cyclophosphamide), and 8 initially received BEV alone, followed by BEV with capcitabine, cyclophosphamide, docetaxel, carboplatin, or weekly paclitaxel. A median of 6 cycles (range 1-20) with 196 total doses of BEV was administered. One patient was lost to follow-up after cycle 1. We observed a 16% response rate (all in those treated with BEV alone) with 62.5% of patients demonstrating stable disease. Median OS was 6.9 months, and the median PFS was 5.5 months. Three grade 3 and no grade 4 adverse events were observed. Grade 3 toxicities included hypertension, proteinuria, and enterocutaneous fistula. The fistula occurred after 5 cycles of BEV in a patient who had undergone 7 debulking surgeries prior to BEV. Conclusions.: BEV is generally well tolerated after multiple prior cytotoxic regimens and results in significant clinical benefit among women with recurrent ovarian cancer. © 2006 Elsevier Inc. All rights reserved.