Everolimus Implicated in Case of Severe Gastrointestinal Hemorrhage

Abstract

Breast cancer remains the leading cause of cancer and the third leading cause of cancer related deaths among our population with an estimated number of 246,660 new cases and 40,450 deaths in 2016. With treatment advancements, including targeted agents such as Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, survivability and quality of life continue to improve. However, with the use of these agents come adverse effects, some of which are still being characterized. Our case demonstrates recurrent episodes of gastrointestinal bleeding in a 60-year-old woman being treated with Everolimus for progressive metastatic breast cancer. On endoscopy, bleeding was secondary to erosive gastritis. Previous case reports have described bleeding due to gastric antral vascular ectasia (GAVE), which was described in two prior reported cases. In our case, bleeding also occurred on a reduced dose of Everolimus compared to what is previously reported (5 mg versus 10 mg). As a result of her gastrointestinal bleeding, she required multiple endoscopic interventions including argon plasma coagulation and multipolar heater probe to achieve hemostasis. This is the first case reported of gastrointestinal bleeding not consistent with GAVE and occurring while being on a reduced dose of Everolimus. It is important to document our case so that the Gastroenterology and Hematology communities can be educated and made aware for their patient populations on Everolimus.

Life-Threatening Everolimus-Associated Erosive-Hemorrhagic Gastropathy in a Liver Transplant Patient

“…A) bleeding antral angiodysplasias that were treated with argon plasma coagulation (everolimus 3.5 mg/ daily); B) gastric antral bleeding erosions in a context of hyperemic and fragile mucosa (everolimus 4 mg/daily); C) endoscopic appearance 1 week after everolimus discontinuation. it presented as hemorrhagic colitis, while in the only case reported in a LT patient no definite source of bleeding was identified after repeated lower and upper GI tract endoscopic examinations [6][7][8][9][10] . Our patient presented for the first time, even considering his pre-LT clinical history, with GI bleeding that was initially interpreted as multifactorial: he was on prophylactic antiplatelet therapy with ASA and initially had concomitant endoscopic findings of gastric and colic angiodysplasia, all of them endoscopically apparently non-bleeding in the investigations performed after the first episode of melena and anemia.…”

“…Rare cases of severe hemorrhage have been reported in the literature during treatment with mTOR inhibitors, either everolimus or temsirolimus [6][7][8][9][10][11] . In five cases previously documented in the literature the patients were undergoing chemotherapy (2 cases for breast cancer, 2 cases for renal cancer, 1 case for metastatic neuroendocrine tumor), and in just one report the patient had previously undergone LT [6][7][8][9][10][11] . In four of the 5 cases bleeding originated from the upper digestive tract, and in one case Figure 1.…”

“…The most common adverse effects of everolimus include stomatitis, diarrhea, asthenia, rash, fatigue, vomiting and dry mouth, while gastrointestinal bleeding is not reported among them 4,5 . Very few cases of gastrointestinal (GI) bleeding associated with use of everolimus during chemotherapy consisting in mTOR inhibitors have been documented in the literature, and only one case in a LT patient was reported after two years of everolimus and concomitant introduction of apixaban [6][7][8][9][10] .…”

Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success

“…Cases of severe gastrointestinal (GI) bleeding during targeted therapy with everolimus have been reported [29–31]. In two of these reports, gastric antral vascular ectasia (GAVE) was identified as the likely cause of bleeding [29, 30]; GI bleeding was successfully treated with endoscopic hemostasis using argon plasma coagulation after treatment discontinuation.…”

“…In two of these reports, gastric antral vascular ectasia (GAVE) was identified as the likely cause of bleeding [29, 30]; GI bleeding was successfully treated with endoscopic hemostasis using argon plasma coagulation after treatment discontinuation. In another case, GI bleeding was associated with treatment initiation and resolved following discontinuation [31]. Endoscopy revealed that the bleeding was secondary to erosive gastritis, and several endoscopic interventions were needed to achieve hemostasis.…”