A Phase II Study of Capecitabine, Oxaliplatin, and Bevacizumab in the Treatment of Metastatic Esophagogastric Adenocarcinomas

Abstract

Background. Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated the safety, tolerability, and efficacy of the combination capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas.Methods. Thirty-seven patients with metastatic or unresectable gastric/gastroesophageal junction tumors were enrolled and treated with capecitabine 850 mg/m 2 BID on days 1-14, and oxaliplatin 130 mg/m 2 with bevacizumab 15 mg/kg on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Neuropilin-1 (NRP1) and -2 (NRP2) mRNA expression was evaluated in archived tumor.

Neoadjuvant therapy of bevacizumab in combination with oxaliplatin and capecitabine (XELOX) for patients with metastatic colorectal cancer with unresectable liver metastases: a phase II, open‐label, single‐arm, noncomparative trial

“…44 Yet, another biomarker that was shown to be inversely correlated with PFS after treatment with bevacizumab, oxaliplatin and capecitabine regimen is neoropilin-2 (NRP-2). 45 Patients with metastatic/unresectable gastroesophageal junction tumors having greater NRP-2 expression had shorter PFS, suggesting the role of NRP-2 in anti-VEGF therapy. 45 Thus, multiple angiogenic biomarkers have prognostic and predictive importance for mCRC patients receiving bevacizumab plus XELOX combination therapy.…”

“…45 Patients with metastatic/unresectable gastroesophageal junction tumors having greater NRP-2 expression had shorter PFS, suggesting the role of NRP-2 in anti-VEGF therapy. 45 Thus, multiple angiogenic biomarkers have prognostic and predictive importance for mCRC patients receiving bevacizumab plus XELOX combination therapy.…”

Predictive biomarkers for targeted and cytotoxic agents in gastric cancer for personalized medicine

“…Moreover, high levels of plasma VEGF-A predicted an improvement in OS (HR = 0.72; 95% CI, 0.57 to 0.93), and low expression of tumor neuropilin-1 also predicted an improvement in OS (HR = 0.75; 95% CI, 0.59 to 0.97) in the bevacizumab group. In contrast, the predictive value of neuropilin-1 was not noted in another phase II trial (36). According to an analysis of AVAGAST subgroups, VEGF-A and neuropilin-1 had the ability to predict OS only in non-Asian patients (37).…”

Angiogenesis inhibitors in gastric and gastroesophageal junction cancer

“…The disease control rate (DCR) was 79 % with 6.6 months of PFS and 11.1 months of OS. Finally, Uronis et al [39] investigated the combination of bevacizumab with capecitabine and oxaliplatin in primary metastatic esophagogastric adenocarcinomas (RR 51 %, PFS 7.2 months, OS 10.8 months).…”

“…For both biomarkers, subgroup analyses demonstrated significance only in patients from non-Asian regions. Finally, an exploratory analysis of a phase II trial of bevacizumab in combination with capecitabine and oxaliplatin showed that tumor expression of NRP-1 and NRP-2 was assessed and correlated with outcome [39]. However, the small sample size and the absence of a control group do not allow for any conclusions to be drawn regarding the predictive effect of these biomarkers.…”