Avastin for neaodjuvant treatment or for metastatic esophageal cancer – pro

For esophageal cancer, bevacizumab is in the early stages of clinical development. Most trials have been limited to GE adenocarcinomas, given the life-threatening hemoptysis described in bevacizumab-treated patients with squamous cell carcinoma of the lung. A multi-center phase II study of irinotecan, cisplatin, and bevacizumab in 20 patients with unresectable or metastatic gastric or GE adenocarcinoma has shown encouraging preliminary results. Shah and colleagues reported an 87% control rate (PR/SD). Of the 10 patients with measurable disease who completed at least two cycles, the investigators reported PRs in five (50%), minor PRs in four (40%), and stable disease in one. The combination therapy was well tolerated, although, as detailed in a recent update, six (25%) of 24 patients developed thromboembolic events, one patient had a gastric perforation, and another had a near perforation on imaging. No patients had significant bleeding.
Given that most patients with locally advanced esophageal cancer are treated with concurrent chemoradiation, there may be a possible integrative role for VEGF blockade. Neoadjuvant chemoradiation has a minimal effect on the angiogenic tumor profile (VEGF, von Willebrand factor, CD68, macrophage infiltration), portending a bad prognosis. VEGF blockade reduces tumor interstitial pressure and vascular permeability, thus enhancing radiation and delivery of chemotherapy to tumors.he radiosensitizing effect of VEGF antibody has been demonstrated in several xenograft models, including those of glioma, colon, lung, and esophageal adenocarcinomaVEGF antibody with radiation induced supra-additive tumor growth delay and sustained cell death over a significant period of time in vivo (4–6 months) without schedule dependency . Moreover, radiation potentiation occurred under both hypoxic and normal tumor oxygenation. These preclinical data were explored further in a recent phase I rectal cancer clinical trial with neoadjuvant 5-FU, radiation, and bevacizumab. The addition of bevacizumab to concurrent chemoradiotherapy was feasible and had no significant additive toxicities. A preoperative trial with bevacizumab, cisplatin, irinotecan, and concurrent radiation in locally advanced esophageal adenocarcinoma is open at Memorial Sloan-Kettering Cancer Center later this year.

There is not sufficient credible evidence and no guidelines recommendations to consider Avastin medically necessary in combination or alone for esophageal cancer.

J. Wang, F. Liu, H. Gao, W. Wei, X. Zhang, Y. Liang, and Y. Cheng he Symptom-to-Treatment Delay and Stage at the Time of Treatment in Cancer of Esophagus pn. J. Clin. Oncol., February 5, 2008; (2008)

Shah MA, Ilson D, Saltz E et al. A multicenter phase II study of irinotecan(CPT), cisplatin(CIS), and bevacizumab(BEV) in patients with unresectable or metastatic gastric or gastroesophageal(GEJ) adenocarcinoma. Proc Am Soc Clin Oncol 2005;23:314s.

Shah MA, Ilson D, Kelsen DP. Thromboembolic events in gastric cancer: high incidence in patients receiving irinotecan- and bevacizumab-based therapy. J Clin Oncol 2005;23:2574–2576.

J. Tabernero , T. Macarulla , F. J. Ramos , and J. Baselga
Novel targeted therapies in the treatment of gastric and esophageal cancer
Ann Oncol 16: 1740-1748.

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