Avoiding bevacizumab related gastrointestinal toxicity for recurrent ovarian cancer by careful patient screening

Bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor, has demonstrated activity in recurrent ovarian carcinoma. An incidence of bowel perforation of 11% was reported in a recent phase II trial. A prior study from our institution demonstrated frequent (26%) transmural bowel wall involvement from ovarian cancer among patients who undergo intestinal resection at initial surgery. Since the initial report of this complication, we have limited bevacizumab treatment to patients without: 1) clinical symptoms of bowel obstruction 2) evidence of rectosigmoid involvement on pelvic exam 3) bowel involvement on CT scan.

Patients with advanced recurrent ovarian cancer treated with single agent or combination bevacizumab therapy (15 mg/kg every 21 days) were retrospectively identified. All patients met the above criteria of no apparent bowel involvement. Toxicity was accessed using standard criteria. Objective tumor assessments and CA-125 Rustin Criteria were used to measure response and progression. Response to therapy was stratified by the presence or absence of bulky disease.

Twenty-five patients (21 primary ovarian cancers; 4 primary peritoneal) had received a median of 5 (range 2-12) prior chemotherapy regimens and 3 (range 1-6) prior platinum containing regimens. All patients were platinum resistant prior to bevacizumab therapy. Ten patients (40%; 95% CI: (27%, 63%)) received a median of 4 cycles (range 1-24) of bevacizumab as a single agent and 15 patients (60%; 95% CI: (41%, 77%)) received bevacizumab in combination with cytotoxic therapy. Only 4 patients (16%; 95% CI: (6%, 35%)) had bulky disease (defined as any one lesion >5 cm) prior to bevacizumab. The overall response rate (partial response) was 28% (7 patients; 95% CI: (14%, 48%)) with a 20% (2 of 10 patients; 95% CI: (5.7%, 51%)) and 33% (5 of 15 patients; 95% CI: (15%, 58%)) response rate with bevacizumab as single agent therapy and as combination therapy, respectively. Stable disease occurred in 40% (10 patients; 95% CI: (23%, 59%)) overall, with 30% bevacizumab alone (3 of 10 patients; 95% CI: (11%, 60%)) and 47% (7 of 15 patients; 95% CI: (25%, 70%)) when in combination. The median overall survival was 9.6 months (approximate 95% CI: (7.7, infinity). There were no cases of bowel perforation or other grade 3/4 toxicities. Grade 1 and 2 toxicities included proteinuria in 7 patients (36%; 95% CI: (14%, 48%)) and hypertension in 3 patients (12%; 95% CI: (4.2%, 30%)).

Bevacizumab demonstrates activity in recurrent platinum resistant ovarian cancer. No bowel perforations were demonstrated in our patient cohort. Such life threatening intestinal complications may be avoidable by careful patient selection even in a heavily pretreated patient population.