title: [Serum pancreatic enzyme elevation under treatment with sorafenib].
abstract: OBJECTIVE
  Sorafenib is an oral multi-kinase inhibitor of Raf-1, VEGF and PDGF receptors and others, resulting in tumor regression and anti-angiogenesis. We studied serum pancreatic enzyme increase associated with sorafenib treatment.
  
  
  METHODS
  In a phase II study of Japanese patients with metastatic renal cell carcinoma, a total of 131 patients received sorafenib 400 mg twice per day. Serum levels of lipase and amylase were measured on day 7 and every 3-4 weeks thereafter during treatment period. When grade 3 or 4 enzyme abnormalities were observed, ultrasound or computed tomography scan was performed to detect pancreatitis.
  
  
  RESULTS
  The incidence of all-grades lipase and amylase increases were 55. 7% and 38. 2%, respectively, while those of grade 3 or 4 were 30. 5% and 5. 3%, respectively. The majority of these events were observed in the first 3 weeks of sorafenib treatment. Grade 3 or 4 lipase increase was detected in 32 patients (24. 4%)on day 7 measurement. These abnormal elevations spontaneously resolved in all patients. Regarding grade 3 lipase increase, the median time to recovery to grade 2 and 1 were 7 and 14 days, respectively. Three patients required interruption of the treatment. No patient showed any clinical manifestation or abnormal imaging finding suggesting pancreatitis.
  
  
  CONCLUSIONS
  Pancreatic enzyme increases observed frequently under sorafenib treatment were transient and asymptomatic. They were not related to symptomatic pancreatitis.
authors.affiliation: Dept. of Gastroenterology, Graduate School of Comprehensive Human Science, University of Tsukuba.
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Adachi
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Masaru
authors.initials: M
authors.lastname: Murai
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000681:Amylases / Q000097:blood*; D001557:Benzenesulfonates / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008049:Lipase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology*; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D000077157:Sorafenib
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D008049:Lipase; D000681:Amylases