Type I hypersensitivity reactions to intravenous administration of etoposide are
extremely rare. Etoposide is an essential component of several chemotherapy
regimens used in gynecologic oncology, and discontinuation of this drug during a
course of treatment should only be due to severe patient intolerance. We report
the successful use of intravenous etoposide phosphate as a substitute drug in a
patient with a yolk sac tumor who manifested a Type I hypersensitivity to
intravenous etoposide. The patient ultimately completed all 4 cycles of
bleomycin, etoposide, cisplatin (BEP) using etoposide phosphate as a substitute
drug

Amy Armstrong

Article Id

David Starks

Deborah Prinz

Lindsay Means

Robert Debernardo

Steven Waggoner

Case Reports in Obstetrics and Gynecology

English

PubMed

Type I hypersensitivity reactions to intravenous administration of etoposide are extremely rare. Etoposide is an essential component of several chemotherapy regimens used in gynecologic oncology, and discontinuation of this drug during a course of treatment should only be due to severe patient intolerance. We report the successful use of intravenous etoposide phosphate as a substitute drug in a patient with a yolk sac tumor who manifested a Type I hypersensitivity to intravenous etoposide. The patient ultimately completed all 4 cycles of bleomycin, etoposide, cisplatin (BEP) using etoposide phosphate as a substitute drug.</jats:p

Robert DeBernardo

Crossref

Hindawi Publishing CorporationCase Reports in Obstetrics and GynecologyVolume 2011, Article ID 837160, 2 pagesdoi:10.1155/2011/837160Case ReportManagement of a Type I Hypersensitivity Reaction toIV Etoposide in a Woman with a Yolk Sac Tumor: A Case ReportDavid Starks,1 Deborah Prinz,2 Amy Armstrong,2 Lindsay Means,2 Steven Waggoner,2and Robert DeBernardo21MacDonald Women’s Hospital, University Hospitals Case Medical Center, Cleveland, OH 44106, USA2Women’s Health Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USACorrespondence should be addressed to Robert DeBernardo, robert.debernardo@uhhospitals.orgReceived 8 June 2011; Accepted 13 July 2011Academic Editors: J.-H. Nam and A. SemczukCopyright © 2011 David Starks et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Type I hypersensitivity reactions to intravenous administration of etoposide are extremely rare. Etoposide is an essentialcomponent of several chemotherapy regimens used in gynecologic oncology, and discontinuation of this drug during a courseof treatment should only be due to severe patient intolerance. We report the successful use of intravenous etoposide phosphate asa substitute drug in a patient with a yolk sac tumor who manifested a Type I hypersensitivity to intravenous etoposide. The patientultimately completed all 4 cycles of bleomycin, etoposide, cisplatin (BEP) using etoposide phosphate as a substitute drug.1. IntroductionHypersensitivity reaction to intravenous etoposide is a rareside eﬀect and is infrequently reported in the medical liter-ature. Etoposide is an essential component of chemotherapyfor patients with rare gynecologic malignancies such as germcell tumors and gestational trophoblastic disease, In youngpatients for whom etoposide-containing regimens are givenwith curative intent, omitting etoposide from regimens suchas BEP (bleomycin, etoposide, cisplatin) or EMA-CO (etopo-side, methotrexate, actinomycin D, cyclophosphamide, vin-cristine) may compromise eﬃcacy, necessitating second-linetherapy. There are no suitable substitutes for etoposide inthese regimens that have demonstrably similar responserates. We report the first documented case in the gynecologicliterature of a severe type I hypersensitivity reaction toetoposide in a woman being treated for a yolk sac tumorsuccessfully treated with etoposide phosphate.2. CaseA 25 year old with stage IC yolk sac tumor was admitted tothe hospital for her first cycle of BEP. She was premedicatedwith decadron, ondansetron, and acetaminophen. Withinminutes of the etoposide infusion the patient reportedshortness of breath, pruritus, and developed a rash on herface and chest. The patient became hypertensive and desatu-rated to 86% on pulse oximetry. The infusion was stoppedafter only 5mL of etoposide had been administered. Shewas supplemented with oxygen and given diphenhydramineand decadron intravenously, which resolved her symptomsrapidly. The patient was rechallenged after administrationof additional corticosteroids. The etoposide infusion wasinitiated at half the original rate and again the patientimmediately developed shortness of breath, flushing, andhypoxia. The infusion was stopped and the patient’s symp-toms resolved.The following day the patient received an equivalentdose of IV etoposide phosphate, a water-soluble ester ofetoposide after premedication with ranitidine (50mg IV),diphenhydramine (50mg IV), and hydrocortisone (100mgIV). The patient tolerated the infusion well and did notexhibit any further hypersensitivity symptoms. The patientcompleted the prescribed four cycles of BEP using etoposidephosphate with the same regimen of premedication withoutincident, and is currently free of disease.3. DiscussionA type I hypersensitivity reaction to the IV administrationof etoposide is an unusual event impacting less than 1% ofpatients. The etiology is unknown, although it is speculated2 Case Reports in Obstetrics and Gynecologythat patients are reacting to the polysorbate 80 used todissolve etoposide. There have been no documented casesof a hypersensitivity reaction to the administration of oraletoposide, and in animal models, reaction to polysorbatehave been demonstrated to result in the release of histamine[1]. Etoposide phosphate is a water soluble prodrug ofetoposide, and this variant does not require polysorbate80 to enter solution. To date no hypersensitivity reactionto etoposide phosphate has been documented [2]. Thereare few case reports in the literature supporting the useof etoposide phosphate in patients with a hypersensitivityreaction to etoposide [3, 4]. This is the first case report in thegynecologic literature of a patient with a yolk sac tumor anda type I hypersensitivity reaction to etoposide successfullytreated with 4 cycles of IV etoposide phosphate.Although infrequently used by gynecologic oncologists,etoposide is an important agent in treating rare and aggres-sive gynecologic malignancies. Eliminating etoposide in thisregimen would likely negatively impact this patient’s poten-tial for a cure. Alternative strategies included desensitization:increasing the dose of steroid premedication and slowing therate of infusion, but these strategies failed in our patient.Consideration was given to substituting oral etoposide.However, there is no data in the gynecologic or testicularcancer literature to support this and may have compromisedher chance of cure. The use of second-line chemotherapysuch as VAC (vincristine, adriamycin, cyclophosphamide)was also considered but given the lower response rate thisstrategy was abandoned. The use of etoposide phosphate inthis setting seemed wise.We were able to successfully complete four cycles of BEPusing etoposide phosphate, a water soluble prodrug form ofetoposide.We initially premedicated our patient with H1 andH2 blockers and 100mg of IV hydrocortisone 15 minutesbefore and repeated the hydrocortisone dose immediatelyfollowing infusion. After successfully completing the firstcycle of therapy, we premedicated with diphenhydramine,ranitidine, and hydrocortisone prior to infusing the etopo-side phosphate. The patient tolerated treatment withoutfurther incident.Based on our experience with etoposide phosphate inthis patient, we have created a protocol for its use in thesetting of hypersensitivity reactions. While an extremelyrare side eﬀect to the infusion of etoposide, hypersensitivityreactions present a therapeutic challenge with few viablealternatives. Etoposide phosphate, however, appears to be asuitable alternative and should be considered the alternativedrug of choice for patients with a hypersensitivity reaction toIV etoposide.Conflicts of InterestsThe authors have no conflicts of interest or financial rela-tionships to disclose.References[1] A. Eschalier, J. Lavarenne, C. Burtin, M. Renoux, E. Chapuy,and M. Rodriguez, “Study of histamine release induced byacute administration of anti-tumour agents in dogs,” CancerChemotherapy and Pharmacology, vol. 21, pp. 246–250, 1988.[2] L. Schacter, “Etoposide phosphate: what, why, where, andhow?” Seminars in Oncology, vol. 23, no. 6, supplement 13, pp.1–7, 1996.[3] J. Siderov, P. Prasad, R. De Boer, and J. Desai, “Safe administra-tion of etoposide phosphate after hypersensitivity reaction tointravenous etoposide,” British Journal of Cancer, vol. 86, no. 1,pp. 12–13, 2002.[4] K. Collier, C. Schink, A. M. Young, K. How, M. Seckl, andP. Savage, “Successful treatment with etoposide phosphate inpatients with previous etoposide hypersensitivity,” Journal ofOncology Pharmacy Practice, vol. 14, no. 1, pp. 51–55, 2008.Submit your manuscripts athttp://www.hindawi.comStem CellsInternationalHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014MEDIATORSINFLAMMATIONofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Behavioural NeurologyEndocrinologyInternational Journal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Disease MarkersHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014BioMed Research InternationalOncologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Oxidative Medicine and Cellular LongevityHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014PPAR ResearchThe Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Journal ofObesityJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014 Computational and  Mathematical Methods in MedicineOphthalmologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Diabetes ResearchJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Research and TreatmentAIDSHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Gastroenterology Research and PracticeHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Parkinson’s DiseaseEvidence-Based Complementary and Alternative MedicineVolume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

Management of a Type I Hypersensitivity Reaction to IV Etoposide in a Woman with a Yolk Sac Tumor: A Case Report

Etoposide phosphate: what, why, where, and how?”

Safe administration of etoposide phosphate after hypersensitivity reaction to intravenous etoposide,”

Study of histamine release induced by acute administration of anti-tumour agents

Successful treatment with etoposide phosphate in patients with previous etoposide hypersensitivity,”

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Management of a Type I Hypersensitivity Reaction to IV Etoposide in a Woman with a Yolk Sac Tumor: A Case Report

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