A search of Medline, Embase, and PubMed, was done by use of the search terms “targeted therapy”, “tyrosine-kinase inhibitors”, “anti-angiogenic”, “imatinib”, “sunitinib”, “panitumumab”, “erlotinib”, “gefitinib”, “sorafenib”, “cetuximab”, “bevacizumab”, “clinical trials”, “adverse event”, “emergency”, “surgery”, “complication”, “bleeding”, “perforation”, “solid tumour”, and “cancer”. We also identified references from relevant articles on emergency surgical interventions and complications
ReviewEmergency surgery in the era of molecular treatment of solid tumours
Introduction
An important progression in cancer biology was the understanding of the many signalling pathways and metabolic processes contributing to oncogenesis. This progress enabled the identification of several potential molecular targets for anti-cancer therapy. Compared with conventional cytotoxic chemotherapy, so-called molecularly targeted therapy, is characterised by better target selectivity, the possibility for chronic, durable therapy, a better toxicity profile, and (in some cases) oral administration.1 Several new compounds have been tested in clinical trials and a few of these drugs have been approved for the treatment of solid tumours. These drugs induce the death of tumour cells by direct or indirect mechanisms (eg, anti-angiogenic effects). A wider introduction of these drugs into clinical practice will bring new and unexpected adverse events, such as hypothyroidism or bowel perforation (figure 1), due to different mechanisms of action or tumour-drug interactions.2 Oncologists will need to have knowledge of, and preparation for, these adverse events during molecularly targeted therapy of solid tumours. The aim of this Review is to discuss the management of patients on molecularly targeted agents who present with surgical emergencies, as a side-effect of therapy or the progression of underlying, advanced disease.
Section snippets
Clinical applications and adverse events
Targeted therapies for solid tumours are generally small-molecule tyrosine-kinase inhibitors (TKI), such as imatinib, sunitinib, sorafenib, gefitinib, erlotinib, and lapatinib, or monoclonal antibodies, such as cetuximab, trastuzumab, bevacizumab, and panitumumab.3, 4 Some of these agents act on tumour vasculature; disrupting vessel growth by directly inhibiting vascular endothelial growth factor receptor (VEGFR), or acting on other downstream kinases. We tried to find reports addressing
Discussion and further dilemmas
Molecularly targeted therapies have improved the treatment of several types of solid tumours, and the substantial prolongation of progression-free survival has transformed some malignancies into chronic disorders. Compared with cytotoxic chemotherapy, these drugs are believed to be safe, with a favourable toxicity profile, conferred by their mechanism of action—the inhibition of specific targets in tumour cells or the tumour microenvironment. However, some of the biological effects of these
Conclusion
Although emergency surgery associated with disease progression or therapy during molecularly targeted therapy of solid tumours is rare, it can be life-threatening and physicians must be aware of the possibility. Ideally, an experienced oncological surgeon should always be part of the therapeutic team. Targeted therapy with bevacizumab is the most common example of treatment associated with the possibility of bowel perforation. The frequency of emergency operations for GIST is thought to be
Search strategy and selection criteria
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Cited by (43)
Targeted therapy and molecular genetics
2023, DiSaia and Creasman Clinical Gynecologic OncologyAcute Abdomen, Bowel Obstruction, and Fistula
2019, Abeloff’s Clinical OncologyTargeted therapy and molecular genetics
2018, Clinical Gynecologic OncologyGastrointestinal Stromal Tumors: Imaging Features Before and After Treatment
2017, Current Problems in Diagnostic RadiologyCitation Excerpt :Larger tumors may necessitate open resection, whereas smaller tumors may be removed laparoscopically. Tumor manipulation and rupture should be avoided to minimize the risk of peritoneal seeding.5 Preoperative imatinib therapy may also help to decrease the risk of intraoperative bleeding and spillage of tumor cells.17
Surgical emergencies in oncology
2014, Cancer Treatment ReviewsCitation Excerpt :Perforation may result from complications of medicinal treatment such as steroids, NSAIDs, or from complications of chemotherapy, for example neutropenic enterocolitis and severe dehydration resulting in decreased bowel perfusion [15]. Last, some systemic agents, serving as anti-angiogenesic drugs such as bevacizumab for colorectal cancer, or sunitinib and imatinib for gastrointestinal stromal tumors (GIST), have been associated with intestinal perforation [12,15,101]. The evidence in the literature on the treatment of perforation induced by anti-angiogenic drugs is based on case series and there is no common approach for this emergency [102].