Hepatic Failure and Hepatorenal Syndrome Secondary to Erlotinib: A Possible Etiology of Complications in a Patient with Pancreatic Cancer

We would like to present a case in reference to an article entitled "Hepatic failure and hepatorenal syndrome secondary to erlotinib. Safety reminder” previously published in JOP as Pancreas News in November 2008 [1]. Erlotinib is a epidermal growth factor (EGFR) tyrosine kinase inhibitor which is highly expressed and mutated in certain cancers. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor [2]. For the signal to be transmitted, two members of the EGFR family need to come together to form a homodimer. These then use the molecule of ATP to autophosphorylate each other, which causes a conformational change in their intracellular structure exposing a further binding site for binding proteins that cause a signal cascade to the nucleus. By inhibiting the ATP, autophosphorylation is not possible and the signal is stopped. It is approved by the Food and Drug Administration (FDA) for pancreatic cancer and non small cell lung cancer [3, 4, 5, 6]. Most of the cytotoxic drugs side effect profile is not completely known [7]. Erlotinib is predominantly metabolized in the liver via cytochrome P450 system, by the enzyme P450 3A4, and excreted in the bile. Based on the in vitro and in vivo data suggesting that erlotinib is cleared primarily by the liver, it is possible that erlotinib exposure may be increased in patients with hepatic dysfunction. Toxicities associated with erlotinib include rash, diarrhea, fatigue, pneumonitis, AST/ALT elevation, hyperbilirubinemia, [8, 9] renal insufficiency, hemolytic anemia. In less than 1% it causes StevenJohnson like syndrome, eye lash disorders, hepatic failure, hepatorenal syndrome and gastrointestinal perforation. Here we present a case of pancreatic cancer patient who developed hepatic and renal failure possibly from erlotinib. Our patient is a 39-year-old Caucasian man who was transferred from outside hospital to our facility for further evaluation of his cancer. He was working as a pharmacist until mid-March 2010 when he developed symptoms of reflux and night sweats. He went to a walk-in clinic where he also noted a right axillary lymph node. A mammogram showed no breast pathology and core biopsy of the right axillary lymphnode was performed. Pathology revealed poorly differentiated adenocarcinoma of unknown primary. Immunohistochemistry showed strong positivity for cytokeratin 7, focally positivity for keratin-7 and cytokeratin 20, as well as, negativity for transcription termination factor, RNA polymerase I, alphafetoprotein, human chorionic gonadotropin, prostatespecific antigen and ERBB2 (alias Her 2/Neu: v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)). It was weakly positive for estrogen receptor. He was seen by local oncologist. Staging computed tomography scans on April 22 showed mediastinal lymphadenopathy, ascites and multiple liver lesions concerning for metastasis. Laboratory data evaluated on the same day showed CA 19-9 to be 42,332 U/mL. Pathology was felt to be unknown primary possibly from pancreas, but less likely breast cancer. His labs prior to starting chemotherapy were shown in Table 1. He was started on chemotherapy with abraxane 100 mg/m, gemcitabine 800 mg/m, on May 3 and erlotinib 100 mg po everyday from May 3 to May 5. Received June 16, 2010 Accepted June 30, 2010