Pancreatitis associated with newer classes of antineoplastic therapies

Abstract

Newer anticancer therapies including tyrosine kinase inhibitors, immune modulators, immunotherapies, and chemotherapies have been reported to cause acute pancreatitis. This review gathers data from multiple case reports and small case series that associate these agents with pancreatitis. The mechanism of the pancreatitis may be direct toxicity, elevated triglycerides, immune mediated, or injury with direct injection into the liver, pancreas, or its blood supply. As abdominal pain, nausea, vomiting are associated with cancer chemotherapy itself, the diagnosis of acute pancreatitis might be missed.

Management of Acute Pancreatitis Associated With Checkpoint Inhibitors

“…It is estimated that 0.1% to 2% of acute pancreatitis is associated with drugs (see Table 1 for a list of drugs reported to be associated with pancreatitis). The classes of medications that have been noted to be associated with pancreatitis include chemotherapy agents, agents that cause hypertriglyceridemia, hepatic embolization, hyperthermic intraperitoneal chemotherapy, proteasome inhibitors, immune-modulating agents, tyrosine kinase inhibitors, antibody-toxin conjugates, and immune checkpoint inhibitors ( Clamon, Patel, & Mott, 2017 ; Gandhi et al, 2014 ; Jones, Hall, Kaye, & Kaye, 2015 ; Muzaffar, Jia, Liles, Naveed, & Kumari, 2016 ; Sakhri, Ben Salem, Harbi, Fathallah, & Ltaief, 2010; Trivedi & Pitchumoni, 2005 ).…”

“…It has been noted that the incidence of pancreatitis associated with CTLA-4 agents is higher than that associated with PD-1 agents ( George et al, 2018 ). The incidence of pancreatitis associated with PD-1 agents is approximately 1.8% to 2.6%; however, in combined immunotherapy (ipilimumab [Yervoy] and nivolumab [Opdivo]), the incidence can be as high as 6% ( Clamon et al, 2017 ; George et al, 2018 ; Hofmann et al, 2016 ).…”

“…Physical examination findings may include tenderness upon palpation of the abdomen, abdominal distention, hypoactive bowel sounds, or jaundice. In addition, patients may experience hypotension ( Clamon et al, 2017 ). In severe cases, patients may exhibit tachypnea, hypoxemia, tachycardia, or hypotension ( Vege, 2018 ).…”

Updates in drug-induced acute pancreatitis

“…Everolimus and tamoxifen cause elevated serum triglycerides and hypertriglyceridemia can be the underlying mechanism of reported cases of everolimus and tamoxifen pancreatitis [30]. In many case reports and small case series, newer anticancer agents, immune check point inhibitors, tyrosine kinase inhibitors, and proteasome inhibitors have been reported to cause acute pancreatitis [31]. The proposed mechanisms of pancreatitis are immune-mediation direct toxicity or hypertriglyceridemia [31].…”

“…In many case reports and small case series, newer anticancer agents, immune check point inhibitors, tyrosine kinase inhibitors, and proteasome inhibitors have been reported to cause acute pancreatitis [31]. The proposed mechanisms of pancreatitis are immune-mediation direct toxicity or hypertriglyceridemia [31]. In concern to immune check inhibitors, nivolumab-and pembrolizumab-related pancreatitis have been recently reported in 1.8% of patients.…”