Case Report

Acute Pancreatitis Associated with Sorafenib

Authors: Mingqing Li, MD, MS, Sandy Srinivas, MD

Abstract

Since its FDA approval in December 2005, sorafenib (Nexavar®) has been in use for the treatment of metastatic renal cell carcinoma. With this increased use have come reports of adverse effects of sorafenib. To the best of the authors’ knowledge, they are the first to describe an 80-year-old Asian male with a history of metastatic renal cell carcinoma who developed acute pancreatitis confirmed by computed tomography (CT) one month after taking sorafenib 400 mg orally twice a day. Sorafenib was eventually discontinued, and the pancreatitis resolved. The molecular biologic mechanism causing this side effect is discussed. Patients should be informed of this rare but potentially serious adverse effect before initiation of sorafenib therapy. Early recognition of this complication and complete discontinuation of sorafenib are recommended.


Key Points


* Acute pancreatitis may be explained by the role of VEGF in the maintenance of adult pancreatic fenestrated capillaries, regulation of the cell cycle of the acinar cells, and induction of gastrointestinal motility abnormality.


* Early recognition of this complication and complete discontinuation of sorafenib are recommended.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Ratain MJ, Eisen T, Stadler WM et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006;24:2505–2512.
 
2. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004;64:7099–7109.
 
3. Strumberg D, Richly H, Hilger RA, et al. Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 2005;23:965–972.
 
4. Lammert E, Cleaver O, Melton D. Induction of pancreatic differentiation by signals from blood vessels.Science 2001;294:564–567.
 
5. Kamba T, Tam BY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol 2006;290:H560–H576.
 
6. Buchler P, Reber HA, Buchler MW, et al. VEGF-RII influences the prognosis of pancreatic cancer. Ann Surg 2002;236:738–749.
 
7. Partanen TA, Arola J, Saaristo A, et al. VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor, VEGFR-3, in fenestrated blood vessels in human tissues. FASEB J 2000;14:2087–2096.
 
8. Klar E, Messmer K, Warshaw AL, et al. Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy. Br J Surg 1990;77:1205–1210.
 
9. Murr MM, Yang J, Fier A, et al. Regulation of Kupffer cell TNF gene expression during experimental acute pancreatitis: the role of p38-MAPK, ERK1/2, SAPK/JNK, and NF-kappaB. J Gastrointest Surg 2003;7:20–25.
 
10. Ueda T, Takeyama Y, Yasuda T, et al. Vascular endothelial growth factor increases in serum and protects against the organ injuries in severe acute pancreatitis. J Surg Res 2006;134:223–230.