Severe acute pancreatitis following Afatinib treatment in a lung cancer patient

Abstract

Molecular targeted therapy associated pancreatitis was usually reported mild, focal, and managed conservatively with discontinuation.¹ Afatinib is an epidermal growth factor receptor tyrosine kinase inhibitor that is commonly used as the first-line treatment for patients with metastatic non-small-cell lung cancer.² The US food and drug agency had launched the post marketing warning for the adverse reactions of pancreatitis associated with Afatinib.³ However, there are fewer cases reported currently.

Acute pancreatitis is a condition commonly caused by gall bladder stones, chronic alcohol abuse, hypertriglyceridemia, post-endoscopic retrograde cholangiopancreatography, genetic predisposition, or certain medications (such as steroids, sulfonamides, and thiazides).⁴ Autoimmune pancreatitis is characterized by high levels of immunoglobulin G4 antibody.⁵ However, some idiopathic pancreatitis could challenge the diagnosis and treatment.

We are presenting a 59-year-old female patient with a medical history of lung adenocarcinoma, left nasopharyngeal carcinoma, insomnia, and depression. She had been receiving Afatinib treatment for almost 10 months. The daily dosage of Afatinib remained at 30 mg and was not altered when diarrhea, skin rash, and recurrent gritty pain in the right eye were observed. Following the initiation of Afatinib, the patient underwent blood tests for lipase levels (<60.0 U/L). Results showed 22 U/L (23 days), 28 U/L (45 days), and 30 U/L (133 days) post-Afatinib. Due to severe epigastric pain, she was sent to the emergency department. Further abdominal computed tomography (CT) scan showed peripancreatic infiltrations and fluid at the pancreas tail without calcification lesions, which suggested grade D pancreatitis. Her serum aspartate aminotransferase of 20.0 IU/L and alanine aminotransferase of 27.0 IU/L were within normal range. The amylase of 2656.0 U/L (<100.0) and lipase of 2815.0 U/L were extremely elevated. The serum triglyceride level of 251.0 mg/dL was mild elevated. The IgG4 level of 82.9 mg/dL (<135.0) and antinuclear antibody (negative <1:40) were normal. The patient lacked a history of gallbladder stones, and the CT scan revealed no signs of gallbladder stones. Additionally, the alkaline phosphatase and gamma-glutamyl transferase levels measured at 137 U/L (40–150 U/L) and 253 U/L (<38 U/L), respectively, suggest a lower probability of biliary pancreatitis. Upon reviewing her drug history during the period of Afatinib, the listed drugs of short duration use included loratadine, prednisolone, scopolamine, medroxyprogesterone, and diphenhydramine. The administration of Afatinib was halted during the hospitalization. Due to the patient's deteriorating condition, she was transferred to the Medical Intensive Care Unit. Her abdominal pain also improved, and she was able to transition from total parenteral nutrition to oral intake of food successfully (Figure 1). We have monitored the patients for a duration of 6 months without Afatinib re-administration and no instances of acute pancreatitis were observed. In summary, maintaining a high level of awareness and entertaining the suspicion of acute pancreatitis is crucial when patients on Afatinib treatment manifest symptoms like diarrhea or abdominal pain. Although these symptoms might initially seem typical and manageable with symptom-alleviating medications, they could signal drug-induced pancreatic damage that has the potential to escalate into a life-threatening situation.

The authors declare no conflicts of interest.

Written informed consent was obtained from the patient.