Противоопухолевые средства, прием которых ассоциирован с развитием лекарственно-индуцированного панкреатита

Частота лекарственно-индуцированного панкреатита (ЛИП) составляет от  2  до  5% от  всех случаев острого панкреатита (ОП), но значительно чаще он встречается в группах риска – среди детей и ВИЧ-инфицированных больных. Прием ряда лекарственных средств (ЛС) ассоциирован с развитием ЛИП, среди них особое место занимают противоопухолевые ЛС в связи с большой медикосоциальной значимостью онкологических заболеваний и появлением в последние годы большого количества новых противоопухолевых ЛС. Целью настоящей статьи является обзор данных литературы о противоопухолевых ЛС, прием которых ассоциирован с развитием ЛИП. Лекарственно-индуцированный острый панкреатит развился у 1,8% пациентов, получавших ниволумаб или пембролизумаб. Суммарно в 14 исследованиях 1–3-й фаз по изучению эффективности и безопасности ипилимумаба сообщалось о развитии ОП менее чем у 1% испытуемых. С развитием ОП ассоциирована и терапия молекулярно-нацеленными таргетными препаратами, такими как ингибиторы тирозинкиназы (ИТК) или другими представителями класса ингибиторов киназ. В базе данных безопасности лекарств (нежелательных лекарственных реакций) Всемирной организации здравоохранения (the WHO Global Medicines Safety Database – VigiAccess) содержатся сообщения об отдельных клинических случаях развития ОП на фоне лечения ингибиторами протеасом и конъюгатами «антитело-лекарственное средство». Известно, что с развитием панкреатита также ассоциирован прием следующих противоопухолевых ЛС: 6-меркаптопурина, L-аспарагиназы, тамоксифена, цисплатина, цитарабина, ифосфамида, паклитаксела, доцетаксела, оксалиплатина, капецитабина, алкалоидов барвинка, цитозина, цисплатина, интерферона альфа-2b, доксорубицина, тамоксифена, гефитиниба, винорелбина, левамизола, метотрексата, 5-фторурацила, капецитабина, трансретиноевой кислоты. Большинство случаев ЛИП, ассоциированных с приемом противоопухолевых ЛС, заканчивается выздоровлением после отмены препарата-индуктора, однако описаны и случаи тяжелого течения, в т. ч. летальные.

1. Johnston D.H., Cornish A.L. Acute Pancreatitis in Patients Receiving Chlorothiazide. JAMA. 1959;170(17):1054–1056. https://doi.org/10.1001/jama.1959.03010170016003.

2. Zion M.M, Goldberg B., Suzman M.M. Corticotrophin and Cortisone in the Treatment of scleroderma. Q J Med. 1955;24(95):215–227. Available at: https://pubmed.ncbi.nlm.nih.gov/13266985/.

3. Lee J.K., Enns R. Review of Idiopathic Pancreatitis. World J Gastroenterol. 2007;13(47):6296–6313. https://doi.org/10.3748/wjg.v13.i47.6296.

4. Lankisch P.G., Droge M., Gottesleben F. Drug Induced Pancreatitis: Incidence and Severity. Gut. 1995:37(4):565–567. https://doi.org/10.1136/gut.37.4.565.

5. Остроумова О.Д., Качан В.О. Лекарственно-индуцированный панкреатит. Лечебное дело. 2020;(3):14–25. https://doi.org/10.24412/2071-5315-2020-12251.

6. Kale-Pradhan P.B., Wilhelm S.M. Chapter 39: Pancreatitis. In: Tisdale J.E., Miller D.A. (eds). Drug-Induced Diseases: Prevention, Detection, and Management. Bethesda: American Society of Health-System Pharmacists; 2018, pp. 877–904.

7. Mallory A, Kern F Jr. Drug-Induced Pancreatitis: A Critical Review. Gastroenterology. 1980 Apr;78(4):813–820. Available at: https://pubmed.ncbi.nlm.nih.gov/6986321/.

8. Trivedi C.D., Pitchumoni C.S. Drug-Induced Pancreatitis: An Update. J Clin Gastroenterol. 2005;39(8):709–716. https://doi.org/10.1097/01.mcg.0000173929.60115.b4.

9. Badalov N., Baradarian R., Iswara K., Li J., Steinberg W., Tenner S. DrugInduced Acute Pancreatitis: An Evidence-Based Review. Clin Gastroenterol Hepatol. 2007;5(6):648–661. https://doi.org/10.1016/j.cgh.2006.11.023.

10. Naranjo C.A., Busto U., Sellers E.M., Sandor P., Ruiz I., Roberts E.A. et al. A Method for Estimating the Probability of Adverse Drug Reactions. Clin Pharmacol Ther. 1981;30(2):239–245. https://doi.org/10.1038/clpt.1981.154.

11. Сычев Д.А, Остроумова О.Д., Переверзев А.П., Кочетков А.И., Остроумова Т.М., Клепикова М.В. и др. Лекарственно-индуцированные заболевания: подходы к диагностике, коррекции и профилактике. Фармаконадзор. Фарматека. 2020;(6):113–126. https://doi.org/10.18565/pharmateca.2020.6.113-126.

12. Hofmann L., Forschner A., Loquai C., Goldinger S., Zimmer L., Ugurel S. et al. Cutaneous, Gastrointestinal, Hepatic, Endocrine, and Renal Side Effects of Anti-PD-1 Therapy. Eur J Cancer. 2016;60:190–209. https://doi.org/10.1016/j.ejca.2016.02.025.

13. Ibrahim R.A., Berman D.M., DePril V., Humphrey R.W., Chen T., Messina M. et al. Ipilimumab Safety Profile: Summary of Findings From Completed Trials in Advanced Melanoma. J Clin Oncol. 2011;29(15_Suppl):8583. https://doi.org/10.1200/jco.2011.29.15_suppl.8583.

14. Weber J.S., Kähler K.C., Hauschild A. Management of Immune-Related Adverse Events and Kinetics of Response with Ipilimumab. J Clin Oncol. 2012;30(21):2691–2697. https://doi.org/10.1200/JCO.2012.41.6750.

15. Schwaiger T., van den Brandt C., Fitzner B., Zaatreh S., Kraatz F., Dummer A. et al. Autoimmune Pancreatitis in MRL/Mp Mice Is a T Cell-Mediated Disease Responsive to Cyclosporine A and Rapamycin Treatment. Gut. 2014;63(3):494–505. https://doi.org/10.1136/gutjnl-2012-303635.

16. Clamon G., Patel R., Mott S.L. Pancreatitis Associated with Newer Classes of Antineoplastic Therapies. JCSO. 2017;15(3):e135–e141. https://doi.org/10.12788/jcso.0347.

17. Sumimoto K., Uchida K., Kusuda T., Mitsuyama T., Sakaguchi Y., Fukui T. et al. The Role of CD19+ CD24high CD38high and CD19+ CD24high CD27+ Regulatory B Cells in Patients with Type 1 Autoimmune Pancreatitis. Pancreatology. 2014;14(3):193–200. https://doi.org/10.1016/j.pan.2014.02.004.

18. Sevin A., Chen A., Atkinson B. Tyrosine Kinase Inhibitor Induced Pancreatitis. J Oncol Pharm Pract. 2013;19(3):257–260. https://doi.org/10.1177/1078155212457968.

19. Li M., Srinivas S. Acute Pancreatitis Associated with Sorafenib. South Med J. 2007;100(9):909–911. https://doi.org/10.1097/SMJ.0b013e31813c695d.

20. Pezzilli R., Corinaldesi R., Morselli-Labate A.M. Tyrosine Kinase Inhibitors and Acute Pancreatitis. JOP. 2010;11(3):291–293. Available at: http://www.serena.unina.it/index.php/jop/article/view/3836/4278.

21. Ghatalia P., Morgan C.J., Choueiri T.K., Rocha P., Naik G., Sonpavde G. Pancreatitis with Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors. Crit Rev Oncol Hematol. 2015;94(1):136–145. https://doi.org/10.1016/j.critrevonc.2014.11.008.

22. Tirumani S.H., Jagannathan J.P., Shinagare A.B., Kim Kw., Krajewski K.M., Ramaiya N.H. Acute Pancreatitis Associated with Molecular Targeted Therapies: A Retrospective Review of the Clinico-Radiological Features, Management and Outcome. Pancreatology. 2013;13(5):461–467. https://doi.org/10.1016/j.pan.2013.08.001.

23. Russano M., Vincenzi B., Venditti O., D’Onofrio L., Ratta R., Guida F.M. Pazopanib and Pancreatic Toxicity: A Case Report. BMC Res Notes. 2015;8(1):196. https://doi.org/10.1186/s13104-015-1154-4.

24. Kawakubo K., Hata H., Kawakami H., Kuwatani M., Kawahata S., Kubo K. Pazopanib-Induced Severe Acute Pancreatitis. Case Rep Oncol. 2015;8(2):356–358. https://doi.org/10.1159/000439124.

25. Péron J., Khenifer S., Potier V., Vitry T., Pasquet F., Rassat R., Pavic M. Axitinib-Induced Acute Pancreatitis: A Case Report. Anticancer Drugs. 2014;25(4):478–479. https://doi.org/10.1097/CAD.0000000000000076.

26. Engel T., Justo D., Amitai M., Volchek Y., Mayan H. Nilotinib-Associated Acute Pancreatitis. Ann Pharmacother. 2013;47(1):3. https://doi.org/10.1345/aph.1R334.

27. Blum K.A., Christian B., Flynn J.M., Jaglowski S.M., Jones J.A., Maddocks K., Byrd J.C. A Phase I Trial of the Bruton’s Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), in Combination with Rituximab (R) and Bendamustine in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma (NHL). Blood. 2012;120(21):1643. https://doi.org/10.1182/blood.V120.21.1643.1643.

28. Muluneh B., Buie L.W., Collichio F. Vemurafenib-Associated Pancreatitis: Case Report. Pharmacotherapy. 2013;33(4):43–44. https://doi.org/10.1002/phar.1208.

29. Larkin J., Del Vecchio M., Ascierto P.A., Krajsova I., Schachter J., Neyns B. et al. Vemurafenib in Patients with BRAF(V600) Mutated Metastatic Melanoma: An open-Label, Multicentre, Safety Study. Lancet Oncol. 2014;15(4):436–444. https://doi.org/10.1016/S1470-2045(14)70051-8.

30. Varma M.R., Mathew S., Krishnadas D., Vinayakumar K.R. Imatinib-Induced Pancreatitis. Indian J Pharmacol. 2010;42(1):50–52. https://doi.org/10.4103/0253-7613.62407.

31. Palandri F., Castagnetti F., Soverini S., Poerio A., Gugliotta G., Luatti S. et al. Pancreatic Enzyme Elevation in Chronic Myeloid Leukemia Patients Treated with Nilotinib after Imatinib Failure. Haematologica. 2009;94(12):1758– 1761. https://doi.org/doi:10.3324/haematol.2009.010496.

32. Cortes J.E., Kantarjian H., Shah N.P., Bixby D., Mauro M.J., Flinn I. et al. Ponatinib in Refractory Philadelphia Chromosome-Positive Leukemias. N Engl J Med. 2012;367(22):2075–2088. https://doi.org/10.1056/NEJMoa1205127.

33. Wang H.H., Tsui J., Wang X.Y., Liu S.S., Li J. Bortezomib-Induced Acute Pancreatitis in a Patient with Multiple Myeloma. Leuk Lymphoma. 2014;55(6):1404–1405. https://doi.org/10.3109/10428194.2013.831850.

34. Solakoglu T., Akyol P., Guney T., Dilek I., Atalay R., Koseoglu H. et al. Acute Pancreatitis Caused by Bortezomib. Pancreatology. 2013;13(2):189–190. https://doi.org/10.1016/j.pan.2013.01.002.

35. Elouni B., Ben Salem C., Zamy M., Sakhri J., Bouraoui K., Biour M. Bortezomib-Induced Acute Pancreatitis. JOP. 2010;11(3):275–276.

36. Solakoglu T., Akar M., Aktan Kosker T., Buyukasik S., Ersoy O. Is Bortezomib a Rare Cause of Acute Pancreatitis? JOP. 2013;14(6):682–683. https://doi.org/10.6092/1590-8577/1927.

37. Talamo G., Sivik J., Pandey M.K., Mir M.A. Bortezomib-Induced Acute Pancreatitis: Case Report and Review of the Literature. J Oncol Pharm Pract. 2016;22(2):332–334. https://doi.org/10.1177/1078155214563813.

38. Mihaila R.G. A Possible Rare Complication of Bortezomib Treatment, Acute Pancreatitis. Acta Medica Transilvanica. 2013;2:269–171. Available at http://www.amtsibiu.ro/Arhiva/2013/Nr1-en/Mihaila_pdf.pdf.

39. Gupta H., Bansal R., Khanna S., Saxena S. An Unusual Complication of Bortezomib Therapy: Acute Pancreatitis. Indian J Nephr. 2014;24(2):135– 136. https://doi.org/10.4103/0971-4065.127928.

40. Gotoh M., Kitahara T., Sakuta J., Akahane D., Ohyashiki K. Multiple Lipoma with Hyperlipidemia in a Multiple Myeloma Patient Treated with Bortezomib/Dexamethazone. Leuk Res. 2010;34(4):120–121. https://doi.org/10.1016/j.leukres.2009.10.003.

41. Gozzetti A., Fabbri A., Defina M., Chitarrelli I., Bocchia M. Hyperlipidemia in a myeLoma Patient after Bortezomib Treatment. Leuk Res. 2010;34(9):250. https://doi.org/10.1016/j.leukres.2010.03.025.

42. Misselwitz B., Goede J.S., Pestalozzi B.C., Schanz U., Seebach J.D. Hyperlipidemic Myeloma: Review of 53 Cases. Ann Hematol. 2010;89(6):569–577. https://doi.org/10.1007/s00277-009-0849-9.

43. Kortuem K.M., Stewart A.K. Carfilzomib. Blood. 2013;121(6):893–897. https://doi.org/10.1182/blood-2012-10-459883.

44. Urru S.A., Mariotti E., Carta P., Massidda S., Marcias M., Murru R. et al. Acute Pancreatitis Following Brentuximab Vedotin Therapy for Refractory Hodgkin Lymphoma: A Case Report. Drugs R D. 2014;14(1):9–11. https://doi.org/10.1007/s40268-014-0036-x.

45. Gandhi M.D., Evens A.M., Fenske T.S., Hamlin P., Coiffier B., Engert A. et al. Pancreatitis in Patients Treated with Brentuximab Vedotin: A Previously Unrecognized Serious Adverse Event. Blood. 2014;123(18):2895–2897. https://doi.org/10.1182/blood-2014-03-561878.

46. Truven Health Analytics. Micromedex® Clinical Knowledge Suite. Micromedex Solutions. User Guide. 2017. Available at: https://www.periodicos.capes.gov.br/images/documents/Micromedex%20UserGuide.pdf.

47. Haber C.J., Meltzer S.J., Present D.H., Korelitz B.I. Nature and Course of Pancreatitis Caused by 6-Mercaptopurine in the Treatment of Inflammatory Bowel Disease. Gastroenterology. 1986;91(4):982–986. https://doi.org/10.1016/0016-5085(86)90703-1.

48. Herskowitz L.J., Olansky S., Lang P.G. Acute Pancreatitis Associated with Long-Term Azathioprine Therapy. Occurrence in a Patient with Systemic Lupus Erythematosus. Arch Dermatol. 1979;115(2):179. http://doi.org/10.1001/archderm.1979.04010020025009.

49. Sturdevant R.A., Singleton J.W., Deren J.L., Law D.H., McCleery J.L. AzathioprineRelated Pancreatitis in Patients with Crohn’s Disease. Gastroenterology. 1979;77(4/2):883–886. Available at: https://pubmed.ncbi.nlm.nih.gov/38178/

50. Kawanishi H., Rudolph E., Bull F.E. Azathioprine-Induced Acute Pancreatitis. N Engl J Med. 1973;289(7):357. https://doi.org/10.1056/NEJM197308162890708.

51. Paloyan D., Levin B., Simonowitz D. Azathioprine-Associated Acute Pancreatitis. Am J Dig Dis. 1977;22(9):839–840. https://doi.org/10.1007/BF01694518.

52. Niederle B., Bartos V., Hrodek O., Hyniová H. Acute Pancreatitis after Imuran in a Patient with Autoimmune Haemolytic Anaemia. Mater Med Pol. 1978;10(1):60–62. Available at: https://pubmed.ncbi.nlm.nih.gov/642594/.

53. Simons-Ling N., Schachner L., Penneys N., Gorman H., Zillereulo G., Strauss J. Childhood Systemic Lupus Erythematosus. Association with Pancreatitis, Subcutaneous Fat Necrosis, and Calcinosis Cutis. Arch Dermatol. 1983;119(6):491–494. https://doi.org/10.1001/archderm.119.6.491.

54. Tragnone A., Bazzocchi G., Aversa G., Pecorelli M.G., Elmi G., Venerato S., Lanfranchi G.A. Acute Pancreatitis after Azathioprine Treatment for Ulcerative Colitis. Ital J Gastroenterol. 1996;28(2):102–104. Available at: https://pubmed.ncbi.nlm.nih.gov/8782004/.

55. Siwach V., Bansal V., Kumar A., Rao Ch U., Sharma A., Minz M. Post-Renal Transplant Azathioprine-Induced Pancreatitis. Nephrol Dial Transplant. 1999;14(10):2495–2498. https://doi.org/10.1093/ndt/14.10.2495.

56. Castiglione F., Del Vecchio Blanco G., Rispo A., Mazzacca G. Prevention of Pancreatitis by Weekly Amylase Assay in Patients with Crohn’s Disease Treated with Azathioprine. Am J Gastroenterol. 2000;95(9):2394–2395. https://doi.org/10.1111/j.1572-0241.2000.02347.x.

57. Toubanakis C., Batziou E., Sipsas N., Galanopoulos G., Tzivras M., Archimandritis A. Acute Pancreatitis after Long-Term Therapy with Mesalazine, and Hyperamylasaemia Associated with Azathioprine in a Patient with Ulcerative Colitis. Eur J Gastroenterol Hepatol. 2003;15(8):933–934. https://doi.org/10.1097/00042737-200308000-00019.

58. Floyd A., Pedersen L., Nielsen G.L., Thorlacius-Ussing O., Sorensen H.T. Risk of Acute Pancreatitis in Users of Azathioprine: A Population-Based CaseControl Study. Am J Gastroenterol. 2003;98(6):1305–1308. https://doi.org/10.1111/j.1572-0241.2003.07459.x.

59. Bank L., Wright J.P. 6-Mercaptopurine-Related Pancreatitis in 2 Patients with Inflammatory Bowel Disease. Dig Dis Sci. 1984;29(4):357–359. https://doi.org/10.1007/BF01318523.

60. Willert J.R., Dahl G.V., Marina N.M. Recurrent Mercaptopurine-Induced Acute Pancreatitis: A Rare Complication of Chemotherapy for Acute Lymphoblastic Leukemia in Children. Med Pediatr Oncol. 2002;38(1):73–74. https://doi.org/10.1002/mpo.1273.

61. Weersma R.K., Peters F.T., Oostenbrug L.E., van den Berg A.P., van Haastert M., Ploeg R.J. et al. Increased Incidence of Azathioprine-Induced Pancreatitis in Crohn’s Disease Compared with Other Diseases. Aliment Pharmacol Ther. 2004;20(8):843–850. https://doi.org/10.1111/j.1365-2036.2004.02197.x.

62. Nogueira J.R., Freedman M.A. Acute Pancreatitis as a Complication of Imuran Therapy in Regional Enteritis. Gastroenterology. 1972;62(5):1040– 1041. Available at: https://pubmed.ncbi.nlm.nih.gov/5029069/.

63. Lai S.W., Wang Y.C., Wang C.H., Huang T.Y. Acute Pancreatitis and Erythema Nodosum Associated with Azathioprine. QJM. 2012;105(4):363–364. https://doi.org/10.1093/qjmed/hcr041.

64. Halalsheh H., Bazzeh F., Alkayed K., Salami K., Madanat F. 6-MercaptopurineInduced Recurrent Acute Pancreatitis in Children with Acute Lymphoblastic Leukemia/Lymphoma. J Pediatr Hematol Oncol. 2013;35(6):470–472. https://doi.org/10.1097/MPH.0b013e318271c92f.

65. Chaparro M., Ordas I., Cabre E., Garcia-Sanchez V., Bastida G., Penalva M. et al. Safety of Thiopurine Therapy in Inflammatory Bowel Disease: Longterm Follow-up Study of 3931 Patients. IBD. 2013;19(7):1404–1410. https://doi.org/10.1097/MIB.0b013e318281f28f.

66. Weetman R.M., Baehner R.L. Latent Onset of Clinical Pancreatitis in Children Receiving L-Asparaginase Therapy. Cancer. 1974;34(3):780–785. https://doi.org/10.1002/1097-0142(197409)34:33.0.co;2-u.

67. Haskell C.M., Canellos G.P., Leventhal B.G., Carbone P.P., Block J.B., Serpick A.A., Selawry O.S. L-Asparaginase: Therapeutic and Toxic Effects in Patients with Neoplastic Disease. N Engl J Med. 1969;281(19):1028– 1034. https://doi.org/10.1056/NEJM196911062811902.

68. Land V.J., Sutow W.W., Fernbach D.J., Lane D.M., Williams T.E. Toxicity of L-Asparginase in Children with Advanced Leukemia. Cancer. 1972;30(2):339–347. https://doi.org/10.1002/1097-0142(197208)30:2<339::aid-cncr2820300206>3.0.co;2-p.

69. Raja R.A., Schmiegelow K., Albertsen B.K., Prunsild K., Zeller B., Vaitkeviciene G. et al. Asparaginase-Associated Pancreatitis in Children with Acute Lymphoblastic Leukaemia in the NOPHO ALL2008 Protocol. Br J Haematol. 2014;165(1):126–133. https://doi.org/10.1111/bjh.12733.

70. Greenstein R., Nogeire C., Ohnuma T., Greenstein A. Management of Asparaginase Induced Hemorrhagic Pancreatitis Complicated by Pseudocyst. Cancer. 1979;43(2):718–722. https://doi.org/10.1002/1097-0142(197902)43:23.0.co;2-r.

71. Holland J.F., Bast R.C. Jr, Morton D.L., Frei E. III, Kufe D.W., Weichselbaum R.R. (eds). Cancer Medicine. 4th ed. Baltimore: Williams & Wilkins, 1997. Vol. I, 1800 pp., Vol. II, 1800 pp.

72. Pratt C.B., Simone J.V., Zee P., Aur R.J., Johnson W.W. Comparison of Daily versus Weekly L-Asparaginase for the Treatment of Childhood Acute Leukemia. J Pediatr. 1970;77(3):474–483. https://doi.org/10.1016/s0022-3476(70)80023-3.

73. Shaw M.T., Barnes C.C., Madden F.J., Bagshawe K.D. L-Asparaginase and Pancreatitis. Lancet. 1970;2(7675):721. https://doi.org/10.1016/s0140-6736(70)91990-2.

74. Tan C.L., Chiang S.P., Wee K.P. Acute Haemorrhagic Pancreatitis Following L-Asparaginase Therapy in Acute Lymphoblastic Leukaemia – A Case Report. Singapore Med J. 1974;15(4):278–282. Available at: https://pubmed.ncbi.nlm.nih.gov/4533158/.

75. Koniver G.A., Scott J.E. Pancreatitis with Pseudocyst: A Complication of L-Asparaqinase Therapy for Leukemia. Del Med J. 1978;50(6):330–332. Available at: https://pubmed.ncbi.nlm.nih.gov/668953/.

76. Jain R., Ramanan S.V. Iatrogenic Pancreatitis. A Fatal Complication in the Induction Therapy for Acute Lymphocytic Leukemia. Arch Intern Med. 1978;138(11):1726. https://doi.org/10.1001/archinte.138.11.1726.

77. Yang C.M., Hsieh Y.L., Hwang B. Acute Pancreatitis in Association with L-Asparaginase Therapy: Report of One Case. Zhonghua Yi Xue Za Zhi (Taipei). 1993;51(1):74–77. Available at: https://pubmed.ncbi.nlm.nih.gov/8384060/.

78. Sadoff J., Hwang S., Rosenfeld D., Ettinger L., Spigland N. Surgical Pancreatic Complications Induced by L-Asparaginase. J Pediatr Surg. 1997;32(6):860–863. https://doi.org/10.1016/s0022-3468(97)90636-9.

79. Cheung Y.F., Lee C.W., Chan C.F., Chan K.L., Lau Y.L., Yeung C.Y. Somatostatin Therapy in L-Asparaginase-Induced Pancreatitis. Med Pediatr Oncol. 1994;22(6):421–424. https://doi.org/10.1002/mpo.2950220614.

80. Sahu S., Saika S., Pai S.K., Advani S.H. L-Asparaginase (Leunase) Induced Pancreatitis in Childhood Acute Lymphoblastic Leukemia. Pediatr Hematol Oncol. 1998;15(6):533–538. https://doi.org/10.3109/08880019809018315.

81. Garrington T., Bensard D., Ingram J.D., Silliman C.C. Successful Management with Octreotide of a Child with L-Asparaginase Induced Hemorrhagic Pancreatitis. Med Pediatr Oncol. 1998;30(2):106–109. https://doi.org/10.1002/(sici)1096-911x(199802)30:23.0.co;2-m.

82. Hsu Y.J., Chen Y.C., Ho C.L., Kao W.Y., Chao T.Y. Diabetic Ketoacidosis and Persistent Hyperglycemia as Long-Term Complications of L-AsparaginaseInduced Pancreatitis. Zhonghua Yi Xue Za Zhi (Taipei). 2002;65(9):441–445. Available at: https://pubmed.ncbi.nlm.nih.gov/12433031/.

83. Iatrogenic pancreatitis. Br Med J. 1977;2(6094):1043. https://doi.org/10.1136/bmj.2.6094.1043.

84. Jaffe N., Traggis D., Das L., Kim B.S., Won H., Hann L. et al. Comparison of Daily and Twice-Weekly Schedule of L-Asparaginase in Childhood Leukemia. Pediatrics. 1972;49(4):590–595. Available at: https://pediatrics.aappublications.org/content/49/4/590.long.

85. Larsen C.C., Laursen C.B., Dalby K., Graumann O. Splenic Artery Pseudoaneurysm Due to Acute Pancreatitis in a 6-Year-Old boy with Acute Lymphoblastic Leukaemia Treated with L-Aspariginase. BMJ Case Rep. 2014;bcr2013202298. https://doi.org/10.1136/bcr-2013-202298.

86. Treepongkaruna S., Thongpak N., Pakakasama S., Pienvichit P., Sirachainan N., Hongeng S. Acute Pancreatitis in Children with Acute Lymphoblastic Leukemia after Chemotherapy. J Pediatr Hematol Oncol. 2009;31(11):812–815. https://doi.org/10.1097/MPH.0b013e3181b87035.

87. Flores-Calderón J., Exiga-Gonzaléz E., Morán-Villota S., Martín-Trejo J., Yamamoto-Nagano A. Acute Pancreatitis in Children with Acute Lymphoblastic Leukemia Treated with L-Asparaginase. J Pediatr Hematol Oncol. 2009;31(10):790–793. https://doi.org/10.1097/MPH.0b013e3181b794e8.

88. Kearney S.L., Dahlberg S.E., Levy D.E., Voss S.D., Sallan S.E., Silverman L.B. Clinical Course and Outcome in Children with Acute Lymphoblastic Leukemia and Asparaginase-Associated Pancreatitis. Pediatr Blood Cancer. 2009;53(2):162–167. https://doi.org/10.1002/pbc.22076.

89. Oettgen H.F., Stephenson P.A., Schwartz M.K., Leeper R.D., Tallai L., Tan C.C. et al. Toxicity of E. coli L-Asparaginase in Man. Cancer. 1970;25(2):253–278. https://doi.org/10.1002/1097-0142(197002)25:23.0.co;2-u.

90. Zubrod C.G. The Clinical Toxicities of L-Asparaginase in Treatment of Leukemia and Lymphoma. Pediatrics. 1970;45(4):555–559. Available at: https://pediatrics.aappublications.org/content/45/4/555.long.

91. Whitecar J.P. Jr, Bodey G.P., Harris J.E, Freireich E.J. L-Asparaginase. N Engl J Med. 1970;282(13):732–734. https://doi.org/10.1056/NEJM197003262821307.

92. Dolowy W.C., Henson D., Cornet J., Sellin H. Toxic and Antineoplastic Effects of L-Asparaginase. Study of Mice with Lymphoma and Normal Monkeys and Report on a Child with Leukemia. Cancer. 1966;19(12):1813–1819. https://doi.org/10.1002/1097-0142(196612)19:123.0.co;2-e.

93. Earl M. Incidence and Management of Asparaginase-Associated Adverse Events in Patients with Acute Lymphoblastic Leukemia. Clin Adv Hematol Oncol. 2009;7(9):600–606. Available at: https://pubmed.ncbi.nlm.nih.gov/20020672/.

94. McBride C.E., Yavorski R.T., Moses F.M., Robson M.E., Solimando D.A. Jr., Byrd J.C. Acute Pancreatitis Associated with Continuous Infusion Cytarabine Therapy: A Case Report. Cancer. 1996;77(12):2588–2591. https://doi.org/10.1002/(SICI)1097-0142(19960615)77:123.0.CO;2-N.

95. Izraeli S., Adamson P.C., Blaney S.M., Balis F.M. Acute Pancreatitis after Ifosfamide Therapy. Cancer. 1994;74(5):1627–1628. https://doi.org/10.1002/1097-0142(19940901)74:53.0.co;2-u.

96. Puckett J.B., Butler W.M., McFarland J.A. Pancreatitis and Cancer Chemotherapy. Ann Intern Med. 1982;97(3):453. https://doi.org/10.7326/0003-4819-97-3-453_1.

97. Altman A.J., Dinndorf P., Quinn J.J. Acute Pancreatitis in Association with Cytosine Arabinoside Therapy. Cancer. 1982;49(7):1384–1386. https://doi.org/10.1002/1097-0142(19820401)49:73.0.co;2-6.

98. Newman C.E, Ellis D.J. Pancreatitis during Combination Chemotherapy. Clin Oncol. 1979;5(1):83–84. Available at: https://pubmed.ncbi.nlm.nih.gov/421389/

99. Siemers R.F., Friedenberg W.R., Norfleet R.G. High-Dose Cytosine Arabinoside-Associated Pancreatitis. Cancer. 1985;56(8):1940–1942. https://doi.org/10.1002/1097-0142(19851015)56:83.0.co;2-n.

100. McGrail L.H., Sehn L.H., Weiss R.B., Robson M.R., Antin J.H., Byrd J.C. Pancreatitis during Therapy of Acute Myeloid Leukemia: Cytarabine Related? Ann Oncol. 1999;10(11):1373–1376. https://doi.org/10.1023/a:1008342320532.

101. Calvo D.B. 3rd, Patt Y.Z., Wallace S., Chuang V.P., Benjamin R.S., Pritchard J.D. et al. Phase I-II Trial of Percutaneous Intra-Arterial Cis-Diamminedichloro Platinum (II) for Regionally Confined Malignancy. Cancer. 1980;45(6):1278– 1283. https://doi.org/10.1002/1097-0142(19800315)45:63.0.co;2-i.

102. Bunin N., Meyer W.H., Christensen M., Pratt C.B. Pancreatitis Following Cisplatin: A Case Report. Cancer Treat Rep. 1985;69(2):236–237. Available at: https://pubmed.ncbi.nlm.nih.gov/3855700/.

103. Stewart D.J., Feun L.G., Maor M., Leavens M., Burgess M.A., Benjamin R.S., Bodey G.P. Sr. Weekly Cisplatin during Cranial Irradiation for Malignant Melanoma Metastatic to Brain. J Neurooncol. 1983;1(1):49–51. https://doi.org/10.1007/BF00153641.

104. Socinski M.A., Garnick M.B. Acute Pancreatitis Associated with Chemotherapy for Germ Cell Tumors in Two Patients. Ann Intern Med. 1988;108(4):567–568. https://doi.org/10.7326/0003-4819-108-4-567.

105. Yeung K.Y., Haidak D.J., Brown J.A., Anderson D. Metastasis-Induced Acute Pancreatitis in Small Cell Bronchogenic Carcinoma. Arch Intern Med. 1979;139(5):552–554. http://doi.org/10.1001/archinte.1979.03630420042014.

106. Spiegel R.J., Magrath I.T. Tumor Lysis Pancreatitis. Med Pediatr Oncol. 1979;7(2):169–172. https://doi.org/10.1002/mpo.2950070210.

107. Nevalainen T.J. Cytotoxicity of Vinblastine and Vincristine to Pancreatic Acinar Cells. Virchows Arch B Cell Pathol. 1975;18(2):119–127. https://doi.org/10.1007/BF02889240.

108. Ben Kridis W., Khanfir A., Frikha M. Acute Pancreatitis Induced by Anticancer Chemotherapy. Acta Clin Belg. 2013;68(4):309–310. https://doi.org/10.2143/ACB.3351.

109. Garg R., Agarwala S., Bhatnagar V. Acute Pancreatitis Induced by Ifosfamide Therapy. J Pediatr Surg. 2010;45(10):2071–2073. https://doi.org/10.1016/j.jpedsurg.2010.07.028.

110. Kumar D.M., Sundar S., Vasanthan S. A Case of Paclitaxel-Induced Pancreatitis. Clin Oncol (R Coll Radiol). 2003;15(1):35. https://doi.org/10.1053/clon.2002.0170.

111. Hoff P.M., Valero V., Holmes F.A., Whealin H., Hudis C., Hortobagyi G.N. Paclitaxel-Induced Pancreatitis: A Case Report. J Natl Cancer Inst. 1997;89(1):91–93. https://doi.org/10.1093/jnci/89.1.91.

112. Hudis C., Riccio L., Holmes F., Seidman A., Baselga J., Currie V. et al. Phase II Study of Semisynthetic Paclitaxel in Metastatic Breast Cancer. Eur J Cancer. 1997;33(13):2198–2202. https://doi.org/10.1016/s0959-8049(97)00254-2.

113. Butt W., Saadati H., Saif M.W. Oxaliplatin-Induced Pancreatitis: A Case Series. Anticancer Res. 2010;30(12):5113–5115. Available at: https://ar.iiarjournals.org/content/30/12/5113.long.

114. Chan H.Y., Ng C.M., Tiu S.C., Chan A.O., Shek C.C. Hypertriglyceridaemia-Induced Pancreatitis: A Contributory Role of Capecitabine? Hong Kong Med J. 2012;18(6): 526–529. Available at: https://www.hkmj.org/system/files/hkm1212p526.pdf.

115. Yucel H., Warmerdam L.V. Capecitabine-Induced Pancreatitis. J Oncol Pharm Pract. 2010;16(2):133–134. https://doi.org/10.1177/1078155209344650.

116. Jones K.L., Valero V. Capecitabine-Induced Pancreatitis. Pharmacotherapy. 2003;23(8):1076–1078. https://doi.org/10.1592/phco.23.8.1076.32870.

117. Gurzu S., Jung I., Comsulea M., Kadar Z., Azamfirei L., Molnar C. Lethal Cardiotoxicity, Steatohepatitis, Chronic Pancreatitis, and Acute Enteritis Induced by Capecitabine and Oxaliplatin in a 36-Year-Old Woman. Diagn Pathol. 2013;8:150. https://doi.org/10.1186/1746-1596-8-150.

118. Singh V., Devata S., Cheng Y.C. Carboplatin and Docetaxel-Induced Acute Pancreatitis: Brief Report. Int J Clin Oncol. 2010;15(6):642–644. https://doi.org/10.1007/s10147-010-0105-2.

119. Sakhri J., Ben Salem C., Harbi H., Fathallah N., Ltaief R. Severe Acute Pancreatitis due to Tamoxifen-Induced Hypertriglyceridemia with Positive Rechallenge. JOP. 20105;11(4):382–384. Available at: http://www.serena.unina.it/index.php/jop/article/view/3626/3965.

120. Alagozlu H., Cindoruk M., Unal S. Tamoxifen-Induced Severe Hypertriglyceridaemia and Acute Pancreatitis. Clin Drug Investig. 2006;26(5):297–302. https://doi.org/10.2165/00044011-200626050-00007.

121. Lin H.H., Hsu C.H., Chao Y.C. Tamoxifen-Induced Severe Acute Pancreatitis: A Case Report. Dig Dis Sci. 2004;49(6):997–999. https://doi.org/10.1023/b:ddas.0000034561.37401.f2.

122. Athyros V.G., Giouleme O.I., Nikolaidis N.L., Vasiliadis T.V., Bouloukos V.I., Kontopoulos A.G., Eugenidis N.P. Long-Term Follow-Up of Patients with Acute Hypertriglyceridemia-Induced Pancreatitis. J Clin Gastroenterol. 2002;34(4):472–475. https://doi.org/10.1097/00004836-200204000-00020.

123. Artac M., Sari R., Altunbas H., Karayalcin U. Asymptomatic Acute Pancreatitis due to Tamoxifen-Induced Severe Hypertriglyceridemia in a Patient with Diabetes Mellitus and Breast Cancer. J Chemother. 2002;14(3):309–311. https://doi.org/10.1179/joc.2002.14.3.309.

124. Elisaf M.S., Nakou K., Liamis G., Pavlidis N.A. Tamoxifen-Induced Severe Hypertriglyceridemia and Pancreatitis. Ann Oncol. 2000;11(8):1067–1069. https://doi.org/10.1023/a:1008309613082.

125. Colls B.M., George P.M. Severe Hypertriglyceridaemia and Hypercholesterol aemia Associated with Tamoxifen Use. Clin Oncol (R Coll Radiol). 1998;10(4):270–271. https://doi.org/10.1016/s0936-6555(98)80019-8.

126. Noguchi M., Taniya T., Tajiri K., Miwa K., Miyazaki I., Koshino H. et al. Fatal Hyperlipaemia in a Case of Metastatic Breast Cancer Treated by Tamoxifen. Br J Surg. 1987;74(7):586–587. https://doi.org/10.1002/bjs.1800740714.