The use of bevacizumab and concurrent radiation for recurrent gynecologic cancers.

Abstract

5101 Background: To determine the feasibility and preliminary efficacy in a pilot trial of concurrent bevacizumab (Bev) and external beam radiation (EB) for patients with recurrent (rec) gynecologic (gyn) malignancies. Methods: Twenty women were enrolled on a prospective IRB-approved pilot protocol between 2008 and 2010 at BWH/Dana-Farber Cancer Institute. Eligible patients (pts) had rec gyn cancer deemed amenable to EB to a confined area and had no or well-controlled hypertension and no recent vascular events. Standard protocol for these pts would have been EB alone. All pts received Bev 10mg/kg IV q2 weeks for 3 doses (days 1, 15 and 29 during radiation). EB was given daily in 1.8 Gy fractions to a dose of 45 Gy +/- nodal boost +/- brachytherapy. Toxicity (CTCAE version 3.0) was assessed at baseline, weekly during treatment and every 3 months for 1 year after treatment. Study-limiting toxicities (SLT) were defined as any grade 4 thrombotic/embolic/hemorrhagic or hypertensive event, bowel perforation or death; if 3 pts developed an SLT, the treatment would be deemed intolerable. Results: Sixteen women had rec uterine cancer and 4 had rec ovarian cancer. Recurrence sites included vaginal cuff (9), pelvic nodes (3) and supra-pelvic nodes (8). Median follow-up was 13.3 months (range 1.7-26.7).Median time from original diagnosis to relapse was 19 months. All 20 pts completed Bev and EB on schedule. One-year OS was 94% and RFS was 84%. To date, 3 of 20 pts have relapsed, all at distant sites. One pt had a high grade uterine carcinosarcoma and relapsed in the lung; 2 pts had ovarian cancer and relapsed in the lung and small bowel. No other relapses or persistent disease have been noted. Grade 4 lymphopenia was noted in 4 pts. No grade 4 toxicities and no gastrointestinal perforations were observed. Other grade 1 or 2 toxicities included fatigue, diarrhea or low white counts (total n=17). One ovarian cancer pt that relapsed developed a pulmonary embolus > 6 months after completing Bev. Conclusions: Delivering Bev for 3 doses with concurrent EB is safe, tolerable, and provides excellent local tumor control for women with recurrent gyn malignancies. Bev with EB should be considered for gyn malignancies in future trials.