Bevacizumab Combined with Capecitabine and Oxaliplatin in Patients with Advanced Adenocarcinoma of the Small Bowel or Ampulla of Vater: a Single Center, Open-label, Phase 2 Study

Abstract

Background

Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). We conducted a phase II trial to evaluate the benefit of adding bevacizumab to CAPOX.

Patients and Methods

In this phase II, single-arm, single-center, open-label study, we recruited patients aged 18 years and older with untreated advanced SBA or AAC. Patients received capecitabine 750 mg/m2 orally twice daily on days 1–14, oxaliplatin 130mg/m2 intravenously on day 1 and bevacizumab 7.5mg/kg intravenously on day 1 on a 21-day cycle. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary objectives included response rate (RR), overall PFS, overall survival (OS) and toxicity.

Results

Between August 2011 and November 2014, 30 patients were enrolled into the study (M/F 13/17, median age: 63 years [range: 33–78], ECOG PS 0/1/2: 7/20/3). 23 patients (77%) had SBA (18 duodenal, 5 jejunal/ileal) and 7 patients had AAC (5 pancreaticobiliary subtype, 1 mixed subtype, 1 intestinal subtype). The most common grade 3 toxicities observed were fatigue and hypertension (7 [23%] patients each), neutropenia (6 [20%] patients), and diarrhea (3 [10%] patients). The probability of PFS at 6 months was 68% (95% confidence interval [CI] 52% to 88%). The RR was 48.3% with 1 complete response and 13 partial responses; 10 patients had stable disease. At a median follow-up of 25.9 months, median PFS was 8.7 (95% CI 4.9–10.5) months and median OS was 12.9 (95% CI 9.2–19.7) months.

Conclusions

Our results indicate that CAPOX with bevacizumab is an active and well-tolerated regimen for patients with SBA and AAC. These findings support the need for further investigation into the clinical benefit of targeting angiogenesis in SBA and AAC.