Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: A systematic review

Abstract

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.

Survival after Abdominoperineal and Sphincter-Preserving Resection in Nonmetastatic Rectal Cancer: A Population-Based Time-Trend and Propensity Score-Matched SEER Analysis

“…Inevitably, for a portion of patients, that is, those with sphincter-infiltrating tumors, APR is still the only curative treatment. In the future, the application of preoperative, targeted therapy to nonmetastatic rectal cancer could further reduce the nearly stagnating rate [ 36 ].…”

Additional 4-week capecitabine during the resting periods after 6-week neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: long-term oncologic outcomes

“…In addition, many studies about the combination of biologic agents and NCRT have been reported. Although the addition of bevacizumab showed a favorable pCR rate, it is considered to significantly increase toxicity, including enteritis or perforation, and surgical complications, including delayed wound healing, fistula, or bleeding [ 23 ]. A combination of cetuximab has shown disappointing pCR [ 24 ].…”

Contemporary management of locally advanced rectal cancer: Resolving issues, controversies and shifting paradigms

“…As with previous long-term followup results, 8% of the patients had LR; however, the promising local control rates came at the expense of patients' urinary, bowel, and stoma functions. Pursuant to this, the investigators stressed the need for long-term follow-up that would allow for weighing the risks and benefits of targeted multimodality treatments for LARC, specifically the inclusion of patient-reported outcomes and predictors of long-term toxicity in future trials (33).…”