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World J Gastroenterol. May 28, 2014; 20(20): 6081-6091
Published online May 28, 2014. doi: 10.3748/wjg.v20.i20.6081
Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: A systematic review
Lorenzo Fornaro, Chiara Caparello, Caterina Vivaldi, Virginia Rotella, Gianna Musettini, Alfredo Falcone, Editta Baldini, Gianluca Masi
Lorenzo Fornaro, Virginia Rotella, Editta Baldini, Division of Medical Oncology, Azienda USL2 Lucca, 55100 Lucca, Italy
Chiara Caparello, Caterina Vivaldi, Gianna Musettini, Alfredo Falcone, Gianluca Masi, Division of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
Author contributions: Fornaro L was responsible for manuscript design, review of the literature, data analysis and interpretation and manuscript writing; Caparello C, Vivaldi C, Rotella V and Musettini G performed research, analyzed the data and wrote the paper; Falcone A, Baldini E and Masi G contributed to data analysis and interpretation and manuscript writing.
Correspondence to: Dr. Lorenzo Fornaro, Division of Medical Oncology, Azienda USL2 Lucca, Via dell’Ospedale 1, 55100 Lucca, Italy.
Telephone: +39-583-970161 Fax: +39-583-449545
Received: October 29, 2013
Revised: January 18, 2014
Accepted: February 26, 2014
Published online: May 28, 2014

Despite advances in the management of patients with locally advanced, non-metastatic rectal adenocarcinoma (LARC), prognosis remains largely unsatisfactory due to a high rate of distant relapse. In fact, currently available neoadjuvant protocols, represented by fluoropyrimidine-based chemo-radiotherapy (CT-RT) or short-course RT, together with improved surgical techniques, have largely reduced the risk of local relapse, with limited impact on distant recurrence. Available results of phase III trials with additional cytotoxic agents combined with standard CT-RT are disappointing, as no significant reduction in the risk of recurrence has been demonstrated. In order to improve the control of micrometastatic disease, integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach. In particular, the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models, and thus may represent a suitable companion in the neoadjuvant treatment of LARC. Preliminary results of phase I-II clinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection: treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules.

Keywords: Bevacizumab, Chemotherapy, Locally advanced rectal cancer, Neoadjuvant treatment, Radiotherapy

Core tip: Pre-operative treatment of locally advanced rectal cancer is a challenging issue in gastrointestinal oncology. Integrating an antiangiogenic agent such as bevacizumab into neoadjuvant chemo-radiotherapy protocols is a promising approach. We review the different strategies currently under evaluation in order to complement bevacizumab within a multimodality approach for locally advanced rectal cancer patients.