XELOX and bevacizumab followed by single-agent bevacizumab as maintenance therapy as first-line treatment in elderly patients with advanced colorectal cancer: the boxe study.

PURPOSE

The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) in patients with metastatic colorectal cancer (CRC). An increased risk of arterial thromboembolic events has been observed in some trials in older patients, and the potential benefit of a maintenance therapy with bevacizumab alone has not been clearly demonstrated. This phase II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab followed by bevacizumab alone in elderly patients with advanced CRC.

METHODS

Treatment consisted of bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m(2) on day 1, plus capecitabine 1,000 mg/m(2) twice daily on days 1-14, every 3 weeks up to a maximum of 8 cycles. Patients then received maintenance therapy consisting of bevacizumab alone (7.5 mg/kg) once every 3 weeks up to disease progression. The primary study end-points were safety and response rate.

RESULTS

A total of 44 patients were recruited. In an intention-to-treat analysis, the overall response rate was 52% [95% confidence interval (CI) 37 to 68%], with 86% of patients achieving disease control. Median PFS and overall survival were 11.5 months (95% CI 10.0-12.9 months) and 19.3 months (95% CI 16.5-22.1 months), respectively. In all, 10 patients (23%) had grade 3/4 adverse events (AEs), the most common being diarrhea (9%), neutropenia (7%), peripheral neuropathy (7%), and stomatitis (7%). No patients died because of treatment-related AEs. The rate of bevacizumab-related AEs (hypertension, thromboembolic events, and gastrointestinal perforation) was consistent with that reported earlier in the general CRC population.

CONCLUSION

The combination of XELOX and bevacizumab is effective and has a manageable tolerability profile when administered to elderly patients with advanced CRC. Maintenance therapy with single-agent bevacizumab may be considered to extend PFS in this setting of patients.