Etoposide hypersensitivity reactions and outcomes of desensitizations in immediate-type hypersensitivity reactions

Abstract

Aims: This study aims to define characteristics of hypersensitivity reactions with etoposide, and outcomes of desensitizations in immediate-type hypersensitivity rections Methods: This is a retrospective observational study of patients who had hypersensitivity reactions with etoposide from January 2019 to December 2023. Results: A total of 39 patients with lung cancer were included in the study. Ten (25.6%) patients had known other drug allergies and three (7.7%) patients had previous chemotherapeutic hypersensitivity two with paclitaxel and one with docetaxel. Most of the initial hypersensitivities were in the first or second cycle (n=29, 74.4%). Ten (25.4%) patients had hypersensitivity reactions at the first application of etoposide. Thirty (76.9%) patients had immediate-type hypersensitivity reactions. There was no significant difference in terms of patient and initial hypersensitivity characteristics between patients who had immediate or non-immediate type hypersensitivity reactions. Of the 30 patients with immediate-type hypersensitivity reactions, initial reaction was mild in 16 (53.3%) and moderate in 14 (46.7%) patients. Most common symptoms were erythema in 29 (96.7%), dyspnea in 13 (43.3%), chest tightness in 8 (26.7%), discomfortness in 7 (23.3%), and hypertension in 6 (20%). Skin tests were negative in five patients who underwent skin testing. A total of 98 desensitization courses were performed in 27 patients and 3 (11.1%) patients had breakthrough reactions. Conclusion: Most of the hypersensitivity reactions to etoposide are immediate-type and not severe. Desensitization is an effective and safe procedure to manage these reactions. Further research is needed to elucidate the mechanisms of hypersensitivity reactions.

Keywords

• Etoposide
• hypersensitivity
• desensitization
• reaction
• immediate
• chemotherapy

References

1. Pagani M, Bavbek S, Alvarez-Cuesta E, et al. Hypersensitivity reactions to chemotherapy: an EAACI position paper. Allergy. 2022;77(2):388-403.
2. Henwood JM, Brogden RN. Etoposide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in combination chemotherapy of cancer. Drugs. 1990;39(3):438-490.
3. Martinez N, Miyasaki A, Roh L, Koole W, Fernandez KS. A pediatric desensitization protocol for etoposide. Am J Health Syst Pharm. 2020;77(4):277-281.
4. Wright TE, Shah MD, Rider NL, et al. A case series of pediatric oncology patients undergoing successful rapid etoposide desensitization. Pediatr Allergy Immunol. 2019;30(5):579-582.
5. Cotteret C, Rousseau J, Zribi K, Schlatter J. Severe hypersensitivity reaction to etoposide phosphate: a case report. Clin Case Rep. 2020;8(9):1821-1823.
6. Hoetelmans RM, Schornagel JH, ten Bokkel Huinink WW, Beijnen JH. Hypersensitivity reactions to etoposide. Ann Pharmacother. 1996;30(4):367-371.
7. Hudson MM, Weinstein HJ, Donaldson SS, et al. Acute hypersensitivity reactions to etoposide in a VEPA regimen for Hodgkin’s disease. J Clin Oncol. 1993;11(6):1080-1084.
8. Bernstein BJ, Troner MB. Successful rechallenge with etoposide phosphate after an acute hypersensitivity reaction to etoposide. Pharmacotherapy. 1999;19(8):989-991.

9. Siderov J, Prasad P, De Boer R, Desai J. Safe administration of etoposide phosphate after hypersensitivity reaction to intravenous etoposide. Br J Cancer. 2002;86(1):12-13.
10. Lindsay H, Gaynon P. Anaphylactic reaction to etoposide phosphate. Pediatr Blood Cancer. 2012;59(4):765.
11. Ogle KM, Kennedy BJ. Hypersensitivity reactions to etoposide. A case report and review of the literature. Am J Clin Oncol. 1988;11(6):663-665.
12. Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998;316(7143):1511-1514.
13. Zweizig S, Roman LD, Muderspach LI. Death from anaphylaxis to cisplatin: a case report. Gynecol Oncol. 1994;53(1):121-122.
14. Castells M, Sancho-Serra Mdel C, Simarro M. Hypersensitivity to antineoplastic agents: mechanisms and treatment with rapid desensitization. Cancer Immunol Immunother. 2012;61(9):1575-1584.
15. Buhari GK, Kalkan IK, Ates H, et al. Platin desensitizations in thoracic malignancies and risk factors for breakthrough reactions. Allergol Immunopathol (Madr). 2023;51(2):130-136.
16. Demoly P, Adkinson NF, Brockow K, et al. International consensus on drug allergy. Allergy. 2014;69(4):420-437.
17. Brown SG. Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol. 2004;114(2):371-376.
18. Castells MC, Tennant NM, Sloane DE, et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol. 2008;122(3):574-580.
19. Stockton WM, Nguyen T, Zhang L, Dowling TC. Etoposide and etoposide phosphate hypersensitivity in children: incidence, risk factors, and prevention strategies. J Oncol Pharm Pract. 2020;26(2):397-405.
20. Turgay Yagmur I, Guzelkucuk Z, Yarali N, et al. Evaluation of hypersensitivity reactions to cancer chemotherapeutic agents in pediatric patients. Ann Allergy Asthma Immunol. 2020;124(4):350-366.
21. Picard M. Management of hypersensitivity reactions to taxanes. Immunol Allergy Clin North Am. 2017;37(4):679-693.
22. Friedland D, Gorman G, Treat J. Hypersensitivity reactions from taxol and etoposide. J Natl Cancer Inst. 1993;85(24):2036.
23. Leguay Z, Bourneau-Martin D, Pellier I, et al. Successful treatment with etoposide base after an acute hypersensitivity reaction to etoposide phosphate. Pediatr Blood Cancer. 2016;63(3):571.
24. Collier K, Schink C, Young AM, How K, Seckl M, Savage P. Successful treatment with etoposide phosphate in patients with previous etoposide hypersensitivity. J Oncol Pharm Pract. 2008;14(1):51-55.
25. Sambasivan K, Mahmoud S, Kokache A, Seckl M, Savage P. Hypersensitivity reactions to etoposide phosphate. J Oncol Pharm Pract. 2014;20(2):158-160.
26. Babaie D, Shamsian BS, Momtazmanesh N, et al. Rapid desensitization for hypersensitivity reactions to chemotherapeutic drugs; a case series. Iran J Pharm Res. 2019;18(2):1047-1051.
27. Pantin C, Letellez J, Calzas J, Mohedano E. [Indirect identification of hypersensitivity reaction to etoposide mediated by polysorbate 80]. Farm Hosp. 2018;42(1):27-28.
28. Kellie SJ, Crist WM, Pui CH, et al. Hypersensitivity reactions to epipodophyllotoxins in children with acute lymphoblastic leukemia. Cancer. 1991;67(4):1070-1075.
29. Kulhas Celik I, Guvenir H, Buyuktiryaki B, Dibek Misirlioglu E, Ozyoruk D, Toyran M. Successful desensitization to etoposide in a preschool pediatric patient. J Investig Allergol Clin Immunol. 2018;28(5):363-364.
30. Garcia Escallon S, Muniyappa PK, Subramanian S. Successful rapid desensitization to intravenous etoposide using a 14-step protocol. J Allergy Clin Immunol Pract. 2015;3(4):627-628.