- Email: [email protected]
Acute pancreatitis caused by bortezomib
Pancreatology 13 (2013) 189e190
Contents lists available at SciVerse ScienceDirect
Pancreatology journal homepage: www.elsevier.com/locate/pan
Case report
Acute pancreatitis caused by bortezomib Tevfik Solakoglu a, *, Pinar Akyol b, Tekin Guney c, Imdat Dilek c, Roni Atalay a, Huseyin Koseoglu d, Ebru Akin a, Aylin Demirezer Bolat a, Naciye Semnur Buyukasik a, Osman Ersoy d a
Department of Gastroenterology, Ankara Ataturk Research and Education Hospital, Bilkent Street, 06800 Ankara, Turkey Department of Internal Medicine, Ankara Ataturk Research and Education Hospital, Turkey c Department of Haematology, Ankara Ataturk Research and Education Hospital, Turkey d Faculty of Medicine, Department of Gastroenterology, Yildirim Beyazit University, Turkey b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 26 December 2012 Received in revised form 14 January 2013 Accepted 15 January 2013
Drug-induced pancreatitis has been reported rarely. Bortezomib is a selective and reversible proteasome inhibitor used for the treatment of patients with multiple myeloma (MM). Recently, one case report about acute pancreatitis (AP) caused by bortezomib was published in the international literature. Herein we report a case of AP in a 67-year-old male on bortezomib therapy. On the fourth day after the first administration of bortezomib, the patient admitted to the hospital with symptoms of AP. The common etiological factors for AP were all excluded. Than the patient was diagnosed as bortezomib-induced pancreatitis. Copyright Ó 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
Keywords: Bortezomib Acute pancreatitis
1. Introduction Bortezomib is the first proteasome inhibitor approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma (MM) and mantle cell lymphoma [1,2]. It reversibly binds and inhibits the chymotryptic-like proteolytic activity of the proteasome complex [3] Hematological toxicities (especially transient thrombocytopenia), gastrointestinal disturbances and peripheral neuropathy are the most common adverse effects of bortezomib [4]. There has been one report regarding pancreatitis caused by bortezomib treatment in MM [5]. Herein we present the case of a patient with MM, who developed acute pancreatitis (AP) after initiation of bortezomib therapy. 2. Case report A 67 year old man has admitted to the hospital with history of sudden onset, severe abdominal pain radiating to the back. His physical examination revealed a mildly distended abdomen with epigastric tenderness, but other system examinations were normal. From his medical history we have learned that he was diagnosed with MM and bortezomib therapy was started four days ago. He has no history of alcohol use and no family history of pancreatitis. He was not receiving any other drug except bortezomib and dexamethasone. His serum amylase (354 U/L) and lipase (523 U/L) levels * Corresponding author. E-mail address: [email protected] (T. Solakoglu).
were elevated. Viral serology for hepatitis A, B, C virus, cytomegalovirus and herpes virus were all negative. There was no evidence of hypertriglyceridemia, hypercholestrolemia, hypercalcemia on investigations. Abdominal ultrasound was normal. Abdominal computed tomography (CT) scan revealed an edematous pancreas and there were neither peripancreatic fluid collections and nor biliary dilatation. After excluding the other causes of pancreatitis, the patient was diagnosed as AP caused by bortezomib. All drugs were stopped and the patient received symptomatic medical treatment. His clinical status has improved gradually and he was discharged from hospital 3 days after admission. After discontinuing bortezomib, he was restarted on dexamethasone and continued to take dexamethasone 40 mg/daily for 3 days without bortezomib than the treatment regimen for MM was changed. The patient has not suffered a new pancreatic attack for 6 months. 3. Discussion Although numerous drugs have been listed in the etiology of AP, drugs are a relatively uncommon cause of pancreatitis with the incidence of approximately 0.1e2% [6]. Most cases are mild and self-limiting. It is a diagnosis of exclusion and should be considered when other reasonable causes of pancreatitis are not present. 525 different drugs that can induce AP as an adverse reaction are listed in WHO database [6]. In our case, all other possible causes of pancreatitis were ruled out. There was no evidence of gallstones. Serum values of calcium and triglycerides were normal. There was no history of alcohol use and no family history of pancreatitis. The
1424-3903/$ e see front matter Copyright Ó 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pan.2013.01.002
190
T. Solakoglu et al. / Pancreatology 13 (2013) 189e190
patient was not receiving any other medication except bortezomib and dexamethasone. Bortezomib is used for the treatment of patients with MM. It inhibits the intracellular protein degradation pathway (proteasome). Moreover, it alters the levels of numerous intracellular signaling and regulatory proteins and then alters the regulation of cellular processes that may lead to growth arrest or apoptosis. Other intracellular effects of bortezomib and the clinical results are uncertain [1]. Recently, a limited number of studies have shown some evidence about the beneficial effect of bortezomib on AP [7,8]. In one study, the anti-inflammatory effect of bortezomib was reported in acute experimental pancreatitis [7]. In the other study, it was demonstrated that bortezomib was able to reduce the severity of AP in mice [8]. But these studies are not adequate to obtain definitive results in humans. However, there is no clinical studies about this beneficial effect of bortezomib in AP in humans. Conversely bortezomib-induced AP was first described by Elouni et al. [5]. In conclusion, although very infrequent, it should be kept in mind that bortezomib may be associated with life threatening complications like acute pancreatitis.
References [1] Kane RC, Bross PF, Farrell AT, Pazdur R. Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist 2003; 8(6):508e13. [2] Kane RC, Dagher R, Farrell A, Ko CW, Sridhara R, Justice R, et al. Bortezomib for the treatment of mantle cell lymphoma. Clin Cancer Res 2007;13(18 Pt 1): 5291e4. [3] Adams J. The proteasome: a suitable antineoplastic target. Nat Rev Cancer 2004;4(5):349e60. [4] Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003;348(26):2609e17. [5] Elouni B, Ben Salem C, Zamy M, Sakhri J, Bouraoui K, Biour M. Bortezomibinduced acute pancreatitis. JOP 2010;11(3):275e6. [6] Nitsche CJ, Jamieson N, Lerch MM, Mayerle JV. Drug induced pancreatitis. Best Pract Res Clin Gastroenterol 2010;24(2):143e55. [7] Szabolcs A, Biczó G, Rakonczay Z, Tiszlavicz L, Halm G, Wittmann T, et al. Simultaneous proteosome inhibition and heat shock protein induction by bortezomib is beneficial in experimental pancreatitis. Eur J Pharmacol 2009; 616(1e3):270e4. [8] Dong X, Zhan YC, Jiang RY, Xie QP, Peng JP, Wang J, et al. The potential effect of proteasome inhibitor PS-341 on severe acute pancreatitis detected by positron emission tomography in ICR mice. J Surg Res 2010;162(2):193e202.
Contents lists available at SciVerse ScienceDirect
Pancreatology journal homepage: www.elsevier.com/locate/pan
Case report
Acute pancreatitis caused by bortezomib Tevfik Solakoglu a, *, Pinar Akyol b, Tekin Guney c, Imdat Dilek c, Roni Atalay a, Huseyin Koseoglu d, Ebru Akin a, Aylin Demirezer Bolat a, Naciye Semnur Buyukasik a, Osman Ersoy d a
Department of Gastroenterology, Ankara Ataturk Research and Education Hospital, Bilkent Street, 06800 Ankara, Turkey Department of Internal Medicine, Ankara Ataturk Research and Education Hospital, Turkey c Department of Haematology, Ankara Ataturk Research and Education Hospital, Turkey d Faculty of Medicine, Department of Gastroenterology, Yildirim Beyazit University, Turkey b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 26 December 2012 Received in revised form 14 January 2013 Accepted 15 January 2013
Drug-induced pancreatitis has been reported rarely. Bortezomib is a selective and reversible proteasome inhibitor used for the treatment of patients with multiple myeloma (MM). Recently, one case report about acute pancreatitis (AP) caused by bortezomib was published in the international literature. Herein we report a case of AP in a 67-year-old male on bortezomib therapy. On the fourth day after the first administration of bortezomib, the patient admitted to the hospital with symptoms of AP. The common etiological factors for AP were all excluded. Than the patient was diagnosed as bortezomib-induced pancreatitis. Copyright Ó 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
Keywords: Bortezomib Acute pancreatitis
1. Introduction Bortezomib is the first proteasome inhibitor approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma (MM) and mantle cell lymphoma [1,2]. It reversibly binds and inhibits the chymotryptic-like proteolytic activity of the proteasome complex [3] Hematological toxicities (especially transient thrombocytopenia), gastrointestinal disturbances and peripheral neuropathy are the most common adverse effects of bortezomib [4]. There has been one report regarding pancreatitis caused by bortezomib treatment in MM [5]. Herein we present the case of a patient with MM, who developed acute pancreatitis (AP) after initiation of bortezomib therapy. 2. Case report A 67 year old man has admitted to the hospital with history of sudden onset, severe abdominal pain radiating to the back. His physical examination revealed a mildly distended abdomen with epigastric tenderness, but other system examinations were normal. From his medical history we have learned that he was diagnosed with MM and bortezomib therapy was started four days ago. He has no history of alcohol use and no family history of pancreatitis. He was not receiving any other drug except bortezomib and dexamethasone. His serum amylase (354 U/L) and lipase (523 U/L) levels * Corresponding author. E-mail address: [email protected] (T. Solakoglu).
were elevated. Viral serology for hepatitis A, B, C virus, cytomegalovirus and herpes virus were all negative. There was no evidence of hypertriglyceridemia, hypercholestrolemia, hypercalcemia on investigations. Abdominal ultrasound was normal. Abdominal computed tomography (CT) scan revealed an edematous pancreas and there were neither peripancreatic fluid collections and nor biliary dilatation. After excluding the other causes of pancreatitis, the patient was diagnosed as AP caused by bortezomib. All drugs were stopped and the patient received symptomatic medical treatment. His clinical status has improved gradually and he was discharged from hospital 3 days after admission. After discontinuing bortezomib, he was restarted on dexamethasone and continued to take dexamethasone 40 mg/daily for 3 days without bortezomib than the treatment regimen for MM was changed. The patient has not suffered a new pancreatic attack for 6 months. 3. Discussion Although numerous drugs have been listed in the etiology of AP, drugs are a relatively uncommon cause of pancreatitis with the incidence of approximately 0.1e2% [6]. Most cases are mild and self-limiting. It is a diagnosis of exclusion and should be considered when other reasonable causes of pancreatitis are not present. 525 different drugs that can induce AP as an adverse reaction are listed in WHO database [6]. In our case, all other possible causes of pancreatitis were ruled out. There was no evidence of gallstones. Serum values of calcium and triglycerides were normal. There was no history of alcohol use and no family history of pancreatitis. The
1424-3903/$ e see front matter Copyright Ó 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pan.2013.01.002
190
T. Solakoglu et al. / Pancreatology 13 (2013) 189e190
patient was not receiving any other medication except bortezomib and dexamethasone. Bortezomib is used for the treatment of patients with MM. It inhibits the intracellular protein degradation pathway (proteasome). Moreover, it alters the levels of numerous intracellular signaling and regulatory proteins and then alters the regulation of cellular processes that may lead to growth arrest or apoptosis. Other intracellular effects of bortezomib and the clinical results are uncertain [1]. Recently, a limited number of studies have shown some evidence about the beneficial effect of bortezomib on AP [7,8]. In one study, the anti-inflammatory effect of bortezomib was reported in acute experimental pancreatitis [7]. In the other study, it was demonstrated that bortezomib was able to reduce the severity of AP in mice [8]. But these studies are not adequate to obtain definitive results in humans. However, there is no clinical studies about this beneficial effect of bortezomib in AP in humans. Conversely bortezomib-induced AP was first described by Elouni et al. [5]. In conclusion, although very infrequent, it should be kept in mind that bortezomib may be associated with life threatening complications like acute pancreatitis.
References [1] Kane RC, Bross PF, Farrell AT, Pazdur R. Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist 2003; 8(6):508e13. [2] Kane RC, Dagher R, Farrell A, Ko CW, Sridhara R, Justice R, et al. Bortezomib for the treatment of mantle cell lymphoma. Clin Cancer Res 2007;13(18 Pt 1): 5291e4. [3] Adams J. The proteasome: a suitable antineoplastic target. Nat Rev Cancer 2004;4(5):349e60. [4] Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003;348(26):2609e17. [5] Elouni B, Ben Salem C, Zamy M, Sakhri J, Bouraoui K, Biour M. Bortezomibinduced acute pancreatitis. JOP 2010;11(3):275e6. [6] Nitsche CJ, Jamieson N, Lerch MM, Mayerle JV. Drug induced pancreatitis. Best Pract Res Clin Gastroenterol 2010;24(2):143e55. [7] Szabolcs A, Biczó G, Rakonczay Z, Tiszlavicz L, Halm G, Wittmann T, et al. Simultaneous proteosome inhibition and heat shock protein induction by bortezomib is beneficial in experimental pancreatitis. Eur J Pharmacol 2009; 616(1e3):270e4. [8] Dong X, Zhan YC, Jiang RY, Xie QP, Peng JP, Wang J, et al. The potential effect of proteasome inhibitor PS-341 on severe acute pancreatitis detected by positron emission tomography in ICR mice. J Surg Res 2010;162(2):193e202.