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LETTER Hypersensitivity reaction during epirubicin infusion in a cat A 10-year-old, 2·5 kg, female-neutered domestic shorthair cat was prescribed a course of epirubicin hydrochloride (Epirubicin HCl, Baxter, UK) (1 mg/kg by intravenous infusion with 0·9% NaCl over 10 minutes, repeated every 3 weeks for six treatments) as adjunctive chemotherapy to complete histological excision of a high-grade mammary adenocarcinoma. The first infusion resulted in no observable side effects. However towards the end of the second infusion the cat began to retch, vomited once and became acutely dull with evidence of stridor and pharyngeal oedema on oral examination. Neither hypotension nor tachycardia was documented. Treatment was initiated with 5 mg (2 mg/kg) chlorphenamine (Chlorphenamine injectable, Archimedes Pharma, UK) intramuscularly, 1·25 mg (0·5 mg/kg) dexamethasone (Dexadreson, MSD, UK) intravenously and 2·5 mg (1 mg/kg) maropitant (Cerenia; Zoetis, UK) subcutaneously. Oxygen therapy was provided by means of an incubator. Within 10 minutes there was rapid resolution of all clinical signs, including the visible pharyngeal oedema. Two doses of epirubicin were subsequently administered after pre-treatment with chlorphenamine (2 mg/kg) intramuscularly 30 minutes prior to the infusion. No further acute or delayed adverse events occurred. Hypersensitivity reactions of varying mechanisms are well documented with chemotherapeutic agents in humans (ChananKhan et al. 2003, Syrigou et al. 2009, Castells Guitart 2014). Given that the reaction in this case occurred during the second infusion, it is possible that the first dose “sensitized” the cat to the drug and the reaction constituted an antibody-mediated reaction. It is also possible that the reaction may have been due to drug additives, preservatives or excipient rather than the drug itself. While hypersensitivity to doxorubicin/epirubicin infusion has been reported in dogs (Ogilvie et al. 1989, Marrington et al. 2012, Elliott et al. 2013), these reactions appear to be rare. There are no reports of hypersensitivity to epirubicin in cats. In a recent unpublished, retrospective toxicity study of 31 cats receiving epirubicin, none experienced hypersensitivity. One cat however experienced transient, mild respiratory noise which may have been related to hypersensitivity though this remains unknown (Serras et al. 2013).
356
While the risk, is deemed low, cats should be monitored closely for infusion-related reactions when epirubicin is administered as hypersensitivity reactions can be serious and require urgent intervention. It may also be prudent to consider a slower rate of drug infusion. If a reaction occurs then drug administration should be discontinued and treatment with H1-antagonists, corticosteroids and/or adrenaline given, depending on severity. Infusion could be continued if the reaction was mild and the clinical signs controlled but this will be case-dependent. The current case suggests that further doses of epirubicin may be administered after hypersensitivity has been observed following H1 blockade. Further studies would however be required to corroborate this. Given the seemingly low incidence of hypersensitivity during epirubicin infusions in cats, it is not believed that routine premedication is necessary at this time. J. Elliott Willows Veterinary Centre & Referral Service, Highlands Road, Shirley, Solihull, B90 4NH
References Amantea, M., Newman, M. S., Sullivan, T. M., et al. (1999) Relationship of dose intensity to the induction of palmar-plantar erythrodysesthia by pegylated liposomal doxorubicin in dogs. Human & Experimental Toxicology 18, 17-26 Castells Guitart, M. C. (2014) Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century. Journal of Investigational Allergology and Clinical Immunology 24, 72-79; quiz 72 p following 79 Chanan-Khan, A., Szebeni, J., Savay, S., et al. (2003) Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions. Annals of Oncology 14, 1430-1437 Elliott, J. W., Cripps, P., Marrington, A. M., et al. (2013) Epirubicin as part of a multiagent chemotherapy protocol for canine lymphoma. Veterinary and Comparative Oncology 11, 185-198 Lanore, D. & Sayag, D. (2010) Probable cutaneous hypersensitivity to carboplatin single-agent chemotherapy in a dog. Journal of Small Animal Practice 51, 654-656 Marrington, A. M., Killick, D. R., Grant, I. A., et al. (2012) Toxicity associated with epirubicin treatments in a large case series of dogs. Veterinary and Comparative Oncology 10, 113-123 Ogilvie, G. K., Richardson, R. C., Curtis, C. R., et al. (1989) Acute and shortterm toxicoses associated with the administration of doxorubicin to dogs with malignant tumors. Journal of American Veterinary Medical Association 195, 1584-1587 Serras, A., Blackwood, L., Marrington, A., et al. (2013). Toxicity associated with epirubicin treatments in a series of 31 cats. In: Proceedings of the European Society of Veterinary Oncology, Lisbon, Portugal, p 10 Syrigou, E., Makrilia, N., Koti, I., et al. (2009) Hypersensitivity reactions to antineoplastic agents: an overview. Anticancer Drugs 20, 1-6
Journal of Small Animal Practice
•
Vol 56
•
May 2015
•
© 2015 British Small Animal Veterinary Association
LETTER Hypersensitivity reaction during epirubicin infusion in a cat A 10-year-old, 2·5 kg, female-neutered domestic shorthair cat was prescribed a course of epirubicin hydrochloride (Epirubicin HCl, Baxter, UK) (1 mg/kg by intravenous infusion with 0·9% NaCl over 10 minutes, repeated every 3 weeks for six treatments) as adjunctive chemotherapy to complete histological excision of a high-grade mammary adenocarcinoma. The first infusion resulted in no observable side effects. However towards the end of the second infusion the cat began to retch, vomited once and became acutely dull with evidence of stridor and pharyngeal oedema on oral examination. Neither hypotension nor tachycardia was documented. Treatment was initiated with 5 mg (2 mg/kg) chlorphenamine (Chlorphenamine injectable, Archimedes Pharma, UK) intramuscularly, 1·25 mg (0·5 mg/kg) dexamethasone (Dexadreson, MSD, UK) intravenously and 2·5 mg (1 mg/kg) maropitant (Cerenia; Zoetis, UK) subcutaneously. Oxygen therapy was provided by means of an incubator. Within 10 minutes there was rapid resolution of all clinical signs, including the visible pharyngeal oedema. Two doses of epirubicin were subsequently administered after pre-treatment with chlorphenamine (2 mg/kg) intramuscularly 30 minutes prior to the infusion. No further acute or delayed adverse events occurred. Hypersensitivity reactions of varying mechanisms are well documented with chemotherapeutic agents in humans (ChananKhan et al. 2003, Syrigou et al. 2009, Castells Guitart 2014). Given that the reaction in this case occurred during the second infusion, it is possible that the first dose “sensitized” the cat to the drug and the reaction constituted an antibody-mediated reaction. It is also possible that the reaction may have been due to drug additives, preservatives or excipient rather than the drug itself. While hypersensitivity to doxorubicin/epirubicin infusion has been reported in dogs (Ogilvie et al. 1989, Marrington et al. 2012, Elliott et al. 2013), these reactions appear to be rare. There are no reports of hypersensitivity to epirubicin in cats. In a recent unpublished, retrospective toxicity study of 31 cats receiving epirubicin, none experienced hypersensitivity. One cat however experienced transient, mild respiratory noise which may have been related to hypersensitivity though this remains unknown (Serras et al. 2013).
356
While the risk, is deemed low, cats should be monitored closely for infusion-related reactions when epirubicin is administered as hypersensitivity reactions can be serious and require urgent intervention. It may also be prudent to consider a slower rate of drug infusion. If a reaction occurs then drug administration should be discontinued and treatment with H1-antagonists, corticosteroids and/or adrenaline given, depending on severity. Infusion could be continued if the reaction was mild and the clinical signs controlled but this will be case-dependent. The current case suggests that further doses of epirubicin may be administered after hypersensitivity has been observed following H1 blockade. Further studies would however be required to corroborate this. Given the seemingly low incidence of hypersensitivity during epirubicin infusions in cats, it is not believed that routine premedication is necessary at this time. J. Elliott Willows Veterinary Centre & Referral Service, Highlands Road, Shirley, Solihull, B90 4NH
References Amantea, M., Newman, M. S., Sullivan, T. M., et al. (1999) Relationship of dose intensity to the induction of palmar-plantar erythrodysesthia by pegylated liposomal doxorubicin in dogs. Human & Experimental Toxicology 18, 17-26 Castells Guitart, M. C. (2014) Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century. Journal of Investigational Allergology and Clinical Immunology 24, 72-79; quiz 72 p following 79 Chanan-Khan, A., Szebeni, J., Savay, S., et al. (2003) Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions. Annals of Oncology 14, 1430-1437 Elliott, J. W., Cripps, P., Marrington, A. M., et al. (2013) Epirubicin as part of a multiagent chemotherapy protocol for canine lymphoma. Veterinary and Comparative Oncology 11, 185-198 Lanore, D. & Sayag, D. (2010) Probable cutaneous hypersensitivity to carboplatin single-agent chemotherapy in a dog. Journal of Small Animal Practice 51, 654-656 Marrington, A. M., Killick, D. R., Grant, I. A., et al. (2012) Toxicity associated with epirubicin treatments in a large case series of dogs. Veterinary and Comparative Oncology 10, 113-123 Ogilvie, G. K., Richardson, R. C., Curtis, C. R., et al. (1989) Acute and shortterm toxicoses associated with the administration of doxorubicin to dogs with malignant tumors. Journal of American Veterinary Medical Association 195, 1584-1587 Serras, A., Blackwood, L., Marrington, A., et al. (2013). Toxicity associated with epirubicin treatments in a series of 31 cats. In: Proceedings of the European Society of Veterinary Oncology, Lisbon, Portugal, p 10 Syrigou, E., Makrilia, N., Koti, I., et al. (2009) Hypersensitivity reactions to antineoplastic agents: an overview. Anticancer Drugs 20, 1-6
Journal of Small Animal Practice
•
Vol 56
•
May 2015
•
© 2015 British Small Animal Veterinary Association
