Beyond bevacizumab: a review of targeted agents in metastatic small bowel adenocarcinoma
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REVIEW ARTICLE
Beyond bevacizumab: a review of targeted agents in metastatic small bowel adenocarcinoma Danielle Benedict Sacdalan1,2 · Marvin Jonne Mendoza2 · John Paulo Vergara2 · Lance Isidore Catedral2 · Frederic Ivan Ting2 · Louis Mervyn Leones2 · Carlo Miguel Berba2 · Dennis L. Sacdalan2 Received: 15 August 2020 / Accepted: 23 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Small bowel cancers are rare tumors with an incidence 50–100-fold less than colorectal cancer. These tumors carry a poor prognosis. Owing to its rarity, treatment of this disease, particularly in its advanced stages, has not been optimized and is derived mainly from treatment regimens for colorectal cancer. Based on recent studies bevacizumab, an antibody directed against vascular endothelial growth factor and used in the management of metastatic CRC, has been added to treatment guidelines for metastatic small bowel adenocarcinoma. We investigate in this review the evidence behind other targeted treatments that may be beneficial in the treatment of metastatic small bowel adenocarcinoma. These are agents against EGFR, VEGFR-2, HER2, and NTRK as well as immune checkpoint inhibitors. The last class of drugs appears to hold the greatest promise based on the preponderance of evidence supporting its use. However, overall data remains sparse. Results of studies currently underway will be valuable in shedding more light on the management of this aggressive cancer. Keywords Small bowel adenocarcinoma · Targeted therapy · EGFR · HER2 · NTRK · Immunotherapy · Immune checkpoint inhibitors
Introduction Small bowel cancers are rare tumors with an incidence 50–100-fold less than colorectal cancer (CRC). This is in stark contrast to the fact that the small intestine holds the lion’s share of the length and mucosal surface area of the digestive tract [1, 2]. Several mechanisms may explain this: first, the presence of lymphoid aggregates and high levels of IgA contribute to immune surveillance; second, the rapid transit time of material through the small bowel decreases exposure of bowel mucosa to noxious substances; and third, the relatively low levels of microorganisms present in the small intestines protect against bacteria-associated
* Danielle Benedict Sacdalan [email protected] 1
Department of Pharmacology and Toxicology, University of the Philippines Manila College of Medicine, Pedro Gil Street, Manila 1000, Philippines
Division of Medical Oncology, Department of Medicine, Philippine General Hospital and University of the Philippines Manila, Taft Avenue, Manila 1000, Philippines
2
carcinogenesis that has been observed in other sites in the gastrointestinal tract [2–6]. Adenocarcinomas (SBA) comprise, adenocarcinomas (SBA) comprise the largest number (30–40%) of all small bowel cancers, with the duodenum as the most common primary anatomic site [1, 6–11]. Several inherited cancer syndromes have been associated with small bowel cancer. Familial adenomatous polyposis (FAP) is ca
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