Prospective Phase II Study of Neoadjuvant Therapy with Cisplatin, 5-Fluorouracil, and Bevacizumab for Locally Advanced Resectable Esophageal Cancer

Abstract

Background: We investigated the efficacy and tolerability of cisplatin and 5-fluorouracil (5-FU) plus bevacizumab as neoadjuvant therapy for patients with locally advanced resectable esophageal cancer. Patients and Methods: In this prospective phase II study, 22 patients with adenocarcinoma and 6 with squamous cell carcinoma received 2 4-day cycles of bevacizumab 7.5 mg/kg followed by cisplatin 80 mg/m² infusion on day 1 followed by 5-FU 1,000 mg/m² as a 96-h continuous infusion on days 1–4, separated by a 3-week interval. Results: The response rate was 39%, the R0 resection rate was 43%, and the median overall survival (OS) was 17 months. The regimen was well tolerated, with the most common severe toxicities being venous thromboembolism (10%), nausea, and gastrointestinal bleeding (7% each). In 37 patients previously treated with cisplatin and 5-FU alone at our institution and thus serving as historical controls, the response rate was 30%, the R0 resection rate was 44%, and the median OS was 23 months. There was no statistically significant difference between the 2 groups of patients. Conclusion: Adding bevacizumab to cisplatin and 5-FU neoadjuvant chemotherapy was active and well tolerated but did not seem to improve the resection rate or OS compared with prior regimens, including the historical controls at our institution.

Leukocytosis and neutrophilia predict outcome in locally advanced esophageal cancer treated with definitive chemoradiation

“…Attempts to improve locoregional control with higher radiation doses, or locoregional and distant control with concurrent cetuximab or bevacizumab have both failed [10, 11]. Similarly, there were no clear positive improvements when comparing concurrent chemotherapy regimens used.…”

Analysis of pathological complete response rates with paclitaxel-based regimens in trimodality therapy for esophageal cancer

“…The advantage of neoadjuvant chemoradiotherapy prior to resection has been established for both squamous cell carcinoma and adenocarcinoma, and this strategy has become first‐line treatment for locoregionally advanced esophageal cancer in the United States . Fluorouracil (FU)‐ and platinum‐based doublets have been the most studied combination chemotherapies in this disease setting, with 30–50% pathological complete response (pCR) rates at time of resection . More recently, taxane‐based regimens concurrent with radiotherapy have seen increased use as a result of improved patient tolerability .…”

New and emerging combination therapies for esophageal cancer

“…In contrast, addition of angiogenesis inhibitor bevacizumab to neoadjuvant chemotherapy with cisplatin/5-FU showed no extra benefit in patients with SCC (n = 6) or AC (n = 22) in comparison to a historical control group (n = 37) that was treated with cisplatin/5-FU alone 9. In this study, the response rate (RR) was 39%; the R0 resection rate was 43%; and the median OS was 17 months for the experimental group.…”