Skip to main content

Advertisement

Log in

Drug Desensitizations for Chemotherapy: Safety and Efficacy in Preventing Anaphylaxis

  • Anaphylaxis and Drug Allergy (BT Kelly and M Castells, Section Editors)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Hypersensitivity reactions (HSRs) to antineoplastic drugs are increasing due to the expanding use of classical and new drugs in a wide variety of malignancies.

Purpose of Review

The goal of this review is to provide current best practices in the diagnosis and management of HSRs based on data and evidence.

Recent Findings

A plethora of studies have provided evidence of the safety and efficacy of rapid drug desensitizations (RDD) to allow for the reintroduction of antineoplastic drugs following an HSR, based on risk stratification. Recently described biomarkers such as basophil activation test, total IgE, BRCA genotyping, and serum IL-6 can aid in guiding improved precision desensitization protocols. Personalized premedication regimens and protocols have improved RDD safety and outcomes.

Summary

RDD allows for the continued use of chemotherapeutic drugs without impaired drug efficacy. RDD represents the best approach to maintain cancer patients on their most effective treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Brennan PJ, Rodriguez Bouza T, Hsu FI, Sloane DE, Castells MC. Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment. J Allergy Clin Immunol. 2009;124(6):1259–66. https://doi.org/10.1016/j.jaci.2009.09.009.

    Article  CAS  PubMed  Google Scholar 

  2. Caiado J, Brás R, Paulino M, Costa L, Castells M. Rapid desensitization to antineoplastic drugs in an outpatient immunoallergology clinic: outcomes and risk factors. Ann Allergy Asthma Immunol. 2020;125(3):325–33.e1. https://doi.org/10.1016/j.anai.2020.04.017Provides a new risk stratification biomarker for rapid desensitization to platins: total serum IgE.

  3. Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI, et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol. 2008;122(3):574–80. https://doi.org/10.1016/j.jaci.2008.02.044.

    Article  CAS  PubMed  Google Scholar 

  4. Sloane D, Govindarajulu U, Harrow-Mortelliti J, Barry W, Hsu FI, Hong D, et al. Safety, costs, and efficacy of rapid drug desensitizations to chemotherapy and monoclonal antibodies. J Allergy Clin Immunol Pract. 2016;4(3):497–504. https://doi.org/10.1016/j.jaip.2015.12.019.

    Article  PubMed  Google Scholar 

  5. Banerji A, Lax T, Guyer A, Hurwitz S, Camargo CA Jr, Long AA. Management of hypersensitivity reactions to Carboplatin and Paclitaxel in an outpatient oncology infusion center: a 5-year review. J Allergy Clin Immunol Pract. 2014;2(4):428–33. https://doi.org/10.1016/j.jaip.2014.04.010.

    Article  PubMed  Google Scholar 

  6. Otani IM, Wong J, Banerji A. Platinum chemotherapy hypersensitivity: prevalence and management. Immunol Allergy Clin North Am. 2017;37(4):663–77. https://doi.org/10.1016/j.iac.2017.06.003.

    Article  PubMed  Google Scholar 

  7. Wang AL, Patil S, Long AA, Banerji A. Risk-stratification protocol for carboplatin and oxaliplatin hypersensitivity: repeat skin testing to identify drug allergy. Ann Allergy Asthma Immunol. 2015;115(5):422–8. https://doi.org/10.1016/j.anai.2015.07.017.

    Article  CAS  PubMed  Google Scholar 

  8. Madrigal-Burgaleta R, Berges-Gimeno MP, Angel-Pereira D, Ferreiro-Monteagudo R, Guillen-Ponce C, Pueyo C, et al. Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment. Allergy. 2013;68(7):853–61. https://doi.org/10.1111/all.12105.

    Article  CAS  PubMed  Google Scholar 

  9. Madrigal-Burgaleta R, Bernal-Rubio L, Berges-Gimeno MP, Carpio-Escalona LV, Gehlhaar P, Alvarez-Cuesta E. A large single-hospital experience using drug provocation testing and rapid drug desensitization in hypersensitivity to antineoplastic and biological agents. J Allergy Clin Immunol Pract. 2019;7(2):618–35. https://doi.org/10.1016/j.jaip.2018.07.031.

    Article  PubMed  Google Scholar 

  10. Caiado J, Castells M. Presentation and diagnosis of hypersensitivity to platinum drugs. Curr Allergy Asthma Rep. 2015;15(4):9. https://doi.org/10.1007/s11882-015-0515-3.

    Article  CAS  Google Scholar 

  11. Nishihara M, Nishikura K, Morikawa N, Yokoyama S. Factors influencing the appearance of oxaliplatin-induced allergy. Biol Pharm Bull. 2017;40(12):2105–9. https://doi.org/10.1248/bpb.b17-00400.

    Article  CAS  PubMed  Google Scholar 

  12. Castells M, Sancho-Serra Mdel C, Simarro M. Hypersensitivity to antineoplastic agents: mechanisms and treatment with rapid desensitization. Cancer Immunol Immunother. 2012;61(9):1575–84. https://doi.org/10.1007/s00262-012-1273-x.

    Article  CAS  PubMed  Google Scholar 

  13. Feldweg AM, Lee CW, Matulonis UA, Castells M. Rapid desensitization for hypersensitivity reactions to paclitaxel and docetaxel: a new standard protocol used in 77 successful treatments. Gynecol Oncol. 2005;96(3):824–9. https://doi.org/10.1016/j.ygyno.2004.11.043.

    Article  CAS  PubMed  Google Scholar 

  14. Lee C, Gianos M, Klaustermeyer WB. Diagnosis and management of hypersensitivity reactions related to common cancer chemotherapy agents. Ann Allergy Asthma Immunol. 2009;102(3):179–87. https://doi.org/10.1016/S1081-1206(10)60078-6.

    Article  PubMed  Google Scholar 

  15. Picard M, Pur L, Caiado J, Giavina-Bianchi P, Galvão VR, Berlin ST, et al. Risk stratification and skin testing to guide re-exposure in taxane-induced hypersensitivity reactions. J Allergy Clin Immunol. 2016;137(4):1154–64. https://doi.org/10.1016/j.jaci.2015.10.039.

    Article  CAS  PubMed  Google Scholar 

  16. Pradelli J, Verdoire P, Boutros J, Frin A-C, Follana P, Duquesne J, et al. Allergy evaluation of hypersensitivity to platinium salts and taxanes: a six-year experience. J Allergy Clin Immunol Pract. 2020;S2213-2198(19):31066–9. https://doi.org/10.1016/j.jaip.2019.12.032This paper demonstrates the value of skin testing in patients sensitized to platins and taxanes, which should be done at least 2 weeks after the reaction.

  17. Otani IM, Lax T, Long AA, Slawski BR, Camargo CA Jr, Banerji A. Utility of risk stratification for paclitaxel hypersensitivity reactions. J Allergy Clin Immunol Pract. 2018;6(4):1266–73.e2. https://doi.org/10.1016/j.jaip.2017.08.025.

    Article  PubMed  Google Scholar 

  18. Piovano E, Pivetta E, Modaffari P, Martra F, Baima Poma C, Perotto S, et al. A search for predictive factors for hypersensitivity reactions to paclitaxel and platinum salts in chemotherapy for gynecologic pelvic neoplasms. Gynecol Obstet Invest. 2012;74(1):21–7. https://doi.org/10.1159/000336772.

    Article  CAS  PubMed  Google Scholar 

  19. Isabwe GAC, Garcia Neuer M, de Las Vecillas Sanchez L, Lynch DM, Marquis K, Castells M. Hypersensitivity reactions to therapeutic monoclonal antibodies: phenotypes and endotypes. J Allergy Clin Immunol. 2018;142(1):159–70. https://doi.org/10.1016/j.jaci.2018.02.018Provides a novel classification of hypersensitivity to monoclonal antibodies.

  20. Mezzano V, Giavina-Bianchi P, Picard M, Caiado J, Castells M. Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy. BioDrugs. 2014;28:133–44. https://doi.org/10.1007/s40259-013-0066-x.

    Article  CAS  PubMed  Google Scholar 

  21. Picard M, Galvao V. Current knowledge and management of hypersensitivity reactions to monoclonal antibodies. J Allergy Clin Immunol Pract. 2017;5(3):600–9. https://doi.org/10.1016/j.jaip.2016.12.001.

    Article  PubMed  Google Scholar 

  22. Caiado J, Picard M. Diagnostic tools for hypersensitivity to platinum drugs and taxanes: skin testing, specific IgE, and mast cell/basophil mediators. Curr Allergy Asthma Rep. 2014;14(8):451–62. https://doi.org/10.1007/s11882-014-0451-7.

    Article  CAS  PubMed  Google Scholar 

  23. Lenz HJ. Management and preparedness for infusion and hypersensitivity reactions. Oncologist. 2007;12(5):601–9. https://doi.org/10.1634/theoncologist.12-5-601.

    Article  CAS  PubMed  Google Scholar 

  24. Picard M, Castells M. Re-visiting hypersensitivity reactions to taxanes: a comprehensive review. Clin Rev Allergy Immunol. 2015;49(2):177–91. https://doi.org/10.1007/s12016-014-8416-0.

    Article  CAS  PubMed  Google Scholar 

  25. Zanotti KM, Markman M. Prevention and management of antineoplastic-induced hypersensitivity reactions. Drug Saf. 2001;24(10):767–79. https://doi.org/10.2165/00002018-200124100-00005.

    Article  CAS  PubMed  Google Scholar 

  26. Polyzos A, Tsavaris N, Gogas H, Souglakos J, Vambakas L, Vardakas N, et al. Clinical features of hypersensitivity reactions to oxaliplatin: a 10-year experience. Oncology. 2009;76(1):36–41. https://doi.org/10.1159/000178163.

    Article  CAS  PubMed  Google Scholar 

  27. Shao YY, Hu FC, Liang JT, Chiu WT, Cheng AL, Yang CH. Characteristics and risk factors of oxaliplatin-related hypersensitivity reactions. J Formos Med Assoc. 2010;109(5):362–8. https://doi.org/10.1016/S0929-6646(10)60064-2.

    Article  PubMed  Google Scholar 

  28. Brandi G, Pantaleo MA, Galli C, Falcone A, Antonuzzo A, Mordenti P, et al. Hypersensitivity reactions related to oxaliplatin (OHP). Br J Cancer. 2003;89(3):477–81. https://doi.org/10.1038/sj.bjc.6601155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bhargava P, Gammon D, McCormick MJ. Hypersensitivity and idiosyncratic reactions to oxaliplatin. Cancer. 2004;100(1):211–2. https://doi.org/10.1002/cncr.11901.

    Article  PubMed  Google Scholar 

  30. Thomas RR, Quinn MG, Schuler B, Grem JL. Hypersensitivity and idiosyncratic reactions to oxaliplatin. Cancer. 2003;97(9):2301–7. https://doi.org/10.1002/cncr.11379.

    Article  PubMed  Google Scholar 

  31. Park SJ, Lee KY, Park WS, Min SY. Clinical outcomes of reintroducing oxaliplatin to patients with colorectal cancer after mild hypersensitivity reactions. Oncology. 2013;85(6):323–7. https://doi.org/10.1159/000355831.

    Article  CAS  PubMed  Google Scholar 

  32. Kolomeyevskaya NV, Lele SB, Miller A, Riebandt GC, Blum BL, Odunsi KO. Oxaliplatin is a safe alternative option for patients with recurrent gynecologic cancers after hypersensitivity reaction to Carboplatin. Int J Gynecol Cancer. 2015;25(1):42–8. https://doi.org/10.1097/IGC.0000000000000307.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Callahan MB, Lachance JA, Stone RL, Kelsey J, Rice LW, Jazaeri AA. Use of cisplatin without desensitization after carboplatin hypersensitivity reaction in epithelial ovarian and primary peritoneal cancer. Am J Obstet Gynecol. 2007;197(2):199.e1–4. https://doi.org/10.1016/j.ajog.2007.04.044.

    Article  CAS  Google Scholar 

  34. Ottaiano A, Tambaro R, Greggi S, Prato R, Di Maio M, Esposito G, et al. Safety of cisplatin after severe hypersensitivity reactions to carboplatin in patients with recurrent ovarian carcinoma. Anticancer Res. 2003;23(3465--8).

  35. Cernadas JR, Brockow K, Romano A, Aberer W, Torres MJ, Bircher A, et al. General considerations on rapid desensitization for drug hypersensitivity-a consensus statement. Allergy. 2010;65(11):1357–66. https://doi.org/10.1111/j.1398-9995.2010.02441.x.

    Article  CAS  PubMed  Google Scholar 

  36. Hsu Blatman KS, Castells M. Desensitizations for chemotherapy and monoclonal antibodies: indications and outcomes. Curr Allergy Asthma Rep. 2014;14(8):453. https://doi.org/10.1007/s11882-014-0453-5.

    Article  CAS  PubMed  Google Scholar 

  37. McAlpine JN, Kelly MG, O’malley DM, Azodi M, Coombe K, Schwartz PE, et al. Atypical presentations of carboplatin hypersensitivity reactions: characterization and management in patients with gynecologic malignancies. Gynecol Oncol. 2006;103(1):288–92. https://doi.org/10.1016/j.ygyno.2006.03.007.

    Article  CAS  PubMed  Google Scholar 

  38. Castells M. Rapid desensitization of hypersensitivity reactions to chemotherapy agents. Curr Drug Saf. 2006;1(3):243–51. https://doi.org/10.2174/157488606777934413.

    Article  CAS  PubMed  Google Scholar 

  39. Pichler W. Drug hypersensitivity reactions: classification and relationship to T-cell activation. Pichler, WJ (ed): Drug hypersensitivity Basel, Karger, 2007, pp 168-189. 2007.

  40. Shepherd GM. Hypersensitivity reactions to chemotherapeutic drugs. Clin Rev Allergy Immunol. 2003;24(3):253–62. https://doi.org/10.1385/CRIAI:24:3:253.

    Article  CAS  PubMed  Google Scholar 

  41. Markman M, Kennedy A, Webster K, Elson P, Peterson G, Kulp B, et al. Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol. 1999;17(4):1141. https://doi.org/10.1200/JCO.1999.17.4.1141.

    Article  CAS  PubMed  Google Scholar 

  42. Altwerger G, Gressel G, English DP, Nelson WK, Carusillo N, Silasi DA, et al. Platinum desensitization in patients with carboplatin hypersensitivity: a single-institution retrospective study. Gynecol Oncol. 2017;144(1):77–82. https://doi.org/10.1016/j.ygyno.2016.09.027.

    Article  CAS  PubMed  Google Scholar 

  43. Madrigal-Burgaleta R, Berges-Gimeno MP, Angel-Pereira D, Guillen-Ponce C, Sanz ML, Alvarez-Cuesta E. Desensitizing oxaliplatin-induced fever: a case report. J Investig Allergol Clin Immunol. 2013;23(6):435–6.

    CAS  PubMed  Google Scholar 

  44. Castells MC. Hypersensitivity to antineoplastic agents. Curr Pharm Des. 2008;14(27):2892–901. https://doi.org/10.2174/138161208786369803.

    Article  CAS  PubMed  Google Scholar 

  45. Santini D, Tonini G, Salerno A, Vincenzi B, Patti G, Battistoni F, et al. Idiosyncratic reaction after oxaliplatin infusion. Ann Oncol. 2001;12(1):132–3. https://doi.org/10.1023/a:1008366223918.

    Article  CAS  PubMed  Google Scholar 

  46. Silver J, Garcia-Neuer M, Lynch DM, Pasaoglu G, Sloane DE, Castells M. Endophenotyping oxaliplatin hypersensitivity: personalizing desensitization to the atypical platin. J Allergy Clin Immunol Pract. 2020;8(5):1668–80.e2. https://doi.org/10.1016/j.jaip.2020.02.013Provides a novel classification of hypersensitivity to oxaliplatin.

  47. Pagani M, Bavbek S, Dursun AB, Bonadonna P, Caralli M, Cernadas J, et al. Role of skin tests in the diagnosis of immediate hypersensitivity reactions to taxanes: results of a multicenter study. J Allergy Clin Immunol Pract. 2019;7(3):990–7. https://doi.org/10.1016/j.jaip.2018.09.018Multicenter study evaluating the role skin testing to taxanes, which can vary according to the population tested.

  48. Hong D, Sloane D. Hypersensitivity to monoclonal antibodies used for cancer and inflammatory or connective tissue diseases. Ann Allergy Asthma Immunol. 2019;123(1):35–41. https://doi.org/10.1016/j.anai.2019.04.015.

    Article  CAS  PubMed  Google Scholar 

  49. Bonamichi-Santos R, Castells M. Desensitization for drug hypersensitivity to chemotherapy and monoclonal antibodies. Curr Pharm Des. 2016;22(45):6870–80. https://doi.org/10.2174/1381612822666161025154506.

    Article  CAS  PubMed  Google Scholar 

  50. Levin AS, Otani IM, Lax T, Hochberg E, Banerji A. Reactions to rituximab in an outpatient infusion center: a 5-year review. J Allergy Clin Immunol Pract. 2017;5(1):107–13.e1. https://doi.org/10.1016/j.jaip.2016.06.022.

    Article  PubMed  Google Scholar 

  51. Jakubovic BD, Sanchez-Sanchez S, Hamadi S, Lynch DM, Castells M. Interleukin-6: A novel biomarker for monoclonal antibody and chemotherapy-associated hypersensitivity confirms a cytokine-release syndrome phenotype-endotype association. Allergy. 2020;Epub ahead of print. DOI: https://doi.org/10.1111/all.14644. This paper provides the role of serum IL-6 measurements in patients with a cytokine-release syndrome to monoclonal antibodies.

  52. Wong JT, Long A. Rituximab hypersensitivity: evaluation, desensitization, and potential mechanisms. J Allergy Clin Immunol Pract. 2017;5(6):1564–71. https://doi.org/10.1016/j.jaip.2017.08.004.

    Article  PubMed  Google Scholar 

  53. Yang BC, Castells M. Diagnosis and treatment of drug hypersensitivity reactions to biologicals: medical algorithm. Allergy. 2020;Epub ahead of print. DOI: https://doi.org/10.1111/all.14432

  54. Yang BC, Castells M. Rituximab hypersensitivity and desensitization: a personalized approach to treat cancer and connective tissue diseases. Ann Allergy Asthma Immunol. 2019;123(1):11–5. https://doi.org/10.1016/j.anai.2019.03.008.

    Article  PubMed  Google Scholar 

  55. Wong JT, Ling M, Patil S, Banerji A, Long A. Oxaliplatin hypersensitivity: evaluation, implications of skin testing, and desensitization. J Allergy Clin Immunol Pract. 2014;2(1):40–5. https://doi.org/10.1016/j.jaip.2013.08.011.

    Article  PubMed  Google Scholar 

  56. Kemp AM, Kemp S. Pharmacotherapy in refractory anaphylaxis: when intramuscular epinephrine fails. Curr Opin Allergy Clin Immunol. 2014;14(4):371–8. https://doi.org/10.1097/ACI.0000000000000080.

    Article  CAS  PubMed  Google Scholar 

  57. Cardet JC, Castells MC, Hamilton MJ. Immunology and clinical manifestations of non-clonal mast cell activation syndrome. Curr Allergy Asthma Rep. 2013;13(1):10–8. https://doi.org/10.1007/s11882-012-0326-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Payne V, Kam PC. Mast cell tryptase: a review of its physiology and clinical significance. Anaesthesia. 2004;59(7):695–703. https://doi.org/10.1111/j.1365-2044.2004.03757.x.

    Article  CAS  PubMed  Google Scholar 

  59. Picard M, Giavina-Bianchi P, Mezzano V, Castells M. Expanding spectrum of mast cell activation disorders: monoclonal and idiopathic mast cell activation syndromes. Clin Ther. 2013;35(5):548–62. https://doi.org/10.1016/j.clinthera.2013.04.001.

    Article  CAS  PubMed  Google Scholar 

  60. Solano-Solares E, Madrigal-Burgaleta R, Carpio-Escalona LV, Bernal-Rubio L, Berges-Gimeno MP, Alvarez-Cuesta E. Chemotherapy in mastocytosis: administration issues, hypersensitivity, and rapid drug desensitization. J Investig Allergol Clin Immunol. 2017;27(5):315–7. https://doi.org/10.18176/jiaci.0171.

    Article  CAS  PubMed  Google Scholar 

  61. Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215–25. https://doi.org/10.1159/000328760.

    Article  PubMed  Google Scholar 

  62. Lyons JJ. Hereditary alpha tryptasemia: genotyping and associated clinical features. Immunol Allergy Clin North Am. 2018;38(3):483–95. https://doi.org/10.1016/j.iac.2018.04.003.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Jennings SV, Slee V, Zack RM, Verstovsek S, George TI, Shi H, et al. Patient perceptions in mast cell disorders. Immunol Allergy Clin North Am. 2018;38(3):505–25. https://doi.org/10.1016/j.iac.2018.04.006.

    Article  PubMed  Google Scholar 

  64. Brown SG. Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol. 2004;114(2):371–6. https://doi.org/10.1016/j.jaci.2004.04.029.

    Article  PubMed  Google Scholar 

  65. Kang Y, Kwon OY, Jung H, Kang M, An J, Lee JH, et al. Breakthrough reactions during rapid drug desensitization: clinical outcomes and risk factors. Ann Allergy Asthma Immunol. 2019;123(1):48–56. https://doi.org/10.1016/j.anai.2019.05.007.

    Article  PubMed  Google Scholar 

  66. Maindrault-Goebel F, Andre T, Tournigand C, Louvet C, Perez-Staub N, Zeghib N, et al. Allergic-type reactions to oxaliplatin: retrospective analysis of 42 patients. Eur J Cancer. 2005;41(15):2262–7. https://doi.org/10.1016/j.ejca.2005.06.021.

    Article  CAS  PubMed  Google Scholar 

  67. Sliesoraitis S, Chikhale PJ. Carboplatin hypersensitivity. Int J Gynecol Cancer. 2005;15(1):13–8. https://doi.org/10.1111/j.1048-891x.2005.14401.x.

    Article  CAS  PubMed  Google Scholar 

  68. Markman M. The dilemma of carboplatin-associated hypersensitivity reactions in ovarian cancer management. Gynecol Oncol. 2007;107(2):163–5. https://doi.org/10.1016/j.ygyno.2007.06.016.

    Article  CAS  PubMed  Google Scholar 

  69. Sohn KH, Kang DY, Kim JY, Lee SY, Lee KH, Han SW, et al. Incidence and risk of oxaliplatin-induced hypersensitivity in patients with asymptomatic prior exposure: a prospective observational study. J Allergy Clin Immunol Pract. 2018;6(5):1642–8. https://doi.org/10.1016/j.jaip.2017.12.026.

    Article  PubMed  Google Scholar 

  70. Jones R, Ryan M, Friedlander M. Carboplatin hypersensitivity reactions: re-treatment with cisplatin desensitisation. Gynecol Oncol. 2003;89(1):112–5. https://doi.org/10.1016/s0090-8258(03)00066-0.

    Article  CAS  PubMed  Google Scholar 

  71. Shen Y, Li C, Liu W, Mao W, Qian H, Wang H, et al. Clinical analysis of hypersensitivity reactions to oxaliplatin among colorectal cancer patients. Oncol Res. 2018;26(5):801–7. https://doi.org/10.3727/096504017X15139039328978.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Sun T, Li L. A cohort study of hypersensitivity reaction in patients with epithelial ovarian cancer treated with carboplatin. Int J Gynecol Cancer. 2019;29(3):566–71. https://doi.org/10.1136/ijgc-2018-000072.

    Article  PubMed  Google Scholar 

  73. Herrero T, Tornero P, Infante S, Fuentes V, Sanchez MN, De Barrio M, et al. Diagnosis and management of hypersensitivity reactions caused by oxaliplatin. J Investig Allergol Clin Immunol. 2006;16(5):327–30.

    CAS  PubMed  Google Scholar 

  74. Leguy-Seguin V, Jolimoy G, Coudert B, Pernot C, Dalac S, Vabres P, et al. Diagnostic and predictive value of skin testing in platinum salt hypersensitivity. J Allergy Clin Immunol. 2007;119(3):726–30. https://doi.org/10.1016/j.jaci.2006.11.640.

    Article  CAS  PubMed  Google Scholar 

  75. Navo M, Kunthur A, Badell ML, Coffer LW 2nd, Markman M, et al. Evaluation of the incidence of carboplatin hypersensitivity reactions in cancer patients. Gynecol Oncol. 2006;103(2):608–13. https://doi.org/10.1016/j.ygyno.2006.04.002.

    Article  CAS  PubMed  Google Scholar 

  76. Makrilia N, Syrigou E, Kaklamanos I, Manolopoulos L, Saif MW. Hypersensitivity reactions associated with platinum antineoplastic agents: a systematic review. Met Based Drugs. 2010;2010:1–11. https://doi.org/10.1155/2010/207084.

    Article  CAS  Google Scholar 

  77. Jerzak KJ, Deghan Manshadi S, Ng P, Maganti M, McCuaig JM, Bulter M, et al. Prevention of carboplatin-induced hypersensitivity reactions in women with ovarian cancer. J Oncol Pharm Pract. 2018;24(2):83–90. https://doi.org/10.1177/1078155216679028.

    Article  CAS  PubMed  Google Scholar 

  78. Takase N, Matsumoto K, Onoe T, Kitao A, Tanioka M, Kikukawa Y, et al. 4-step 4-h carboplatin desensitization protocol for patients with gynecological malignancies showing platinum hypersensitivity: a retrospective study. Int J Clin Oncol. 2015;20(3):566–73. https://doi.org/10.1007/s10147-014-0731-1.

    Article  CAS  PubMed  Google Scholar 

  79. Gadducci A, Tana R, Teti G, Zanca G, Fanucchi A, Genazzani AR. Analysis of the pattern of hypersensitivity reactions in patients receiving carboplatin retreatment for recurrent ovarian cancer. Int J Gynecol Cancer. 2008;18(4):615–20. https://doi.org/10.1111/j.1525-1438.2007.01063.x.

    Article  CAS  PubMed  Google Scholar 

  80. Lee CW, Matulonis UA, Castells MC. Carboplatin hypersensitivity: a 6-h 12-step protocol effective in 35 desensitizations in patients with gynecological malignancies and mast cell/IgE-mediated reactions. Gynecol Oncol. 2004;95(2):370–6. https://doi.org/10.1016/j.ygyno.2004.08.002.

    Article  CAS  PubMed  Google Scholar 

  81. Lax T, Dizon D, Birrer M, Long A, Del Carmen M, Goodman A, et al. Extended carboplatin infusion does not reduce frequency of hypersensitivity reaction at initiation of retreatment in patients with recurrent platinum-sensitive ovarian cancer. J Allergy Clin Immunol Pract. 2017;5(1):177–8. https://doi.org/10.1016/j.jaip.2016.07.010.

    Article  PubMed  Google Scholar 

  82. Schwartz JR, Bandera C, Bradley A, Brard L, Legare R, Granai CO, et al. Does the platinum-free interval predict the incidence or severity of hypersensitivity reactions to carboplatin? The experience from Women and Infants’ Hospital. Gynecol Oncol. 2007;105(1):81–3. https://doi.org/10.1016/j.ygyno.2006.10.047.

    Article  CAS  PubMed  Google Scholar 

  83. Ma X, Li X. Analysis and treatment of 45 platinum-allergic gynecologic malignant tumors. Int J Clin Oncol. 2018;23(6):1160–6. https://doi.org/10.1007/s10147-018-1326-z.

    Article  CAS  PubMed  Google Scholar 

  84. Zanotti KM, Rybicki LA, Kennedy AW, Belinson JL, Webster KD, Kulp B, et al. Carboplatin skin testing: a skin-testing protocol for predicting hypersensitivity to carboplatin chemotherapy. J Clin Oncol. 2001;19(12):3126–9. https://doi.org/10.1200/JCO.2001.19.12.3126.

    Article  CAS  PubMed  Google Scholar 

  85. Markman M, Zanotti K, Peterson G, Kulp B, Webster K, Belinson J. Expanded experience with an intradermal skin test to predict for the presence or absence of carboplatin hypersensitivity. J Clin Oncol. 2003;21(24):4611–4. https://doi.org/10.1200/JCO.2003.05.539.

    Article  CAS  PubMed  Google Scholar 

  86. Patil SU, Long AA, Ling M, Wilson MT, Hesterberg P, Wong JT, et al. A protocol for risk stratification of patients with carboplatin-induced hypersensitivity reactions. J Allergy Clin Immunol. 2012;129(2):443–7. https://doi.org/10.1016/j.jaci.2011.10.010.

    Article  CAS  PubMed  Google Scholar 

  87. Hesterberg PE, Banerji A, Oren E, Penson RT, Krasner CN, Seiden MV, et al. Risk stratification for desensitization of patients with carboplatin hypersensitivity: clinical presentation and management. J Allergy Clin Immunol. 2009;123(6):1262–7 e1. https://doi.org/10.1016/j.jaci.2009.02.042.

    Article  CAS  PubMed  Google Scholar 

  88. Pagani M, Bonadonna P. Skin test protocol for the prevention of hypersensitivity reactions to oxaliplatin. Anticancer Res. 2014;34(1):537–40.

    CAS  PubMed  Google Scholar 

  89. Limsuwan T, Castells MC. Outcomes and safety of rapid desensitization for chemotherapy hypersensitivity. Expert Opin Drug Saf. 2010;9(1):39–53. https://doi.org/10.1517/14740330903446936.

    Article  CAS  PubMed  Google Scholar 

  90. Syrigou E, Makrilia N, Vassias A, Nikolaidis I, Xyla V, Manolopoulos L, et al. Administration of cisplatin in three patients with carboplatin hypersensitivity: is skin testing useful? Anti-cancer drugs. 2010;21(3):333–8. https://doi.org/10.1097/CAD.0b013e32833418c0.

    Article  CAS  PubMed  Google Scholar 

  91. Pasteur J, Favier L, Pernot C, Guerriaud M, Bernigaud C, Lepage C, et al. Low cross-reactivity between cisplatin and other platinum salts. J Allergy Clin Immunol Pract. 2019;7(6):1894–900. https://doi.org/10.1016/j.jaip.2019.01.057.

    Article  PubMed  Google Scholar 

  92. Elligers KT, Davies M, Sanchis D, Ferencz T, Saif MW. Rechallenge with cisplatin in a patient with pancreatic cancer who developed a hypersensitivity reaction to oxaliplatin. Is skin test useful in this setting? JOP. 2008;9(2):197–202.

    PubMed  Google Scholar 

  93. Enrique E, Malek T, Castello JV, de Mateo JA. Usefulness of skin testing with platinum salts to demonstrate lack of cross-reactivity between carboplatin and cisplatin. Ann Allergy Asthma Immunol. 2008;100(1):86. https://doi.org/10.1016/S1081-1206(10)60410-3.

    Article  PubMed  Google Scholar 

  94. Caiado J, Venemalm L, Pereira-Santos MC, Costa L, Barbosa MP, Castells M. Carboplatin-, oxaliplatin-, and cisplatin-specific IgE: cross-reactivity and value in the diagnosis of carboplatin and oxaliplatin allergy. J Allergy Clin Immunol Pract. 2013;1(5):494–500. https://doi.org/10.1016/j.jaip.2013.06.002.

    Article  PubMed  Google Scholar 

  95. Pagani M, Venemalm L, Bonnadona P, Vescovi PP, Botelho C, Cernadas JR. An experimental biological test to diagnose hypersensitivity reactions to carboplatin: new horizons for an old problem. Jpn J Clin Oncol. 2012;42(4):347–50. https://doi.org/10.1093/jjco/hys006.

    Article  PubMed  Google Scholar 

  96. Ornelas C, Caiado J, Campos Melo A, Pereira Barbosa M, Castells MC. Pereira Dos Santos MC. The contribution of the basophil activation test to the diagnosis of hypersensitivity reactions to oxaliplatin. Int Arch Allergy Immunol. 2018;177(3):274–82. https://doi.org/10.1159/000490313.

    Article  CAS  PubMed  Google Scholar 

  97. Giavina-Bianchi P, Galvao V, Picard M, Caiado J, Castells MC. Basophil activation test is a relevant biomarker of the outcome of rapid desensitization in platinum compounds-allergy. J Allergy Clin Immunol Pract. 2017;5(3):728–36. https://doi.org/10.1016/j.jaip.2016.11.006.

    Article  PubMed  Google Scholar 

  98. Iwamoto T, Hirai H, Yamaguchi N, Kobayashi N, Sugimoto H, Tabata T, et al. Carboplatin-induced severe hypersensitivity reaction: role of IgE-dependent basophil activation and FcεRI. Cancer Sci. 2014;105(11):1472–9. https://doi.org/10.1111/cas.12538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Jean-Luc H. Use of basophil activation test in a case of oxaliplatin hypersensitivity. J Aller Ther. 2011;2:1. https://doi.org/10.4172/2155-6121.1000108.

    Article  Google Scholar 

  100. Iwamoto T, Yuta A, Tabata T, Sugimoto H, Gabazza EC, Hirai H, et al. Evaluation of basophil CD203c as a predictor of carboplatin-related hypersensitivity reaction in patients with gynecologic cancer. Biol Pharm Bull. 2012;35(9):1487–95. https://doi.org/10.1248/bpb.b12-00150.

    Article  CAS  PubMed  Google Scholar 

  101. Jorge S, Swisher EM, Norquist BM, Pennington KP, Gray HJ, Urban RR, et al. Patterns and duration of primary and recurrent treatment in ovarian cancer patients with germline BRCA mutations. Gynecol Oncol Rep. 2019;29:113–7. https://doi.org/10.1016/j.gore.2019.08.001.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Mylavarapu S, Das A, Roy M. Role of BRCA mutations in the modulation of response to platinum therapy. Front Oncol. 2018;8:16. https://doi.org/10.3389/fonc.2018.00016.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Galvão VR, Philips E, Giavina-Bianchi P, Castells MC. Carboplatin-allergic patients undergoing desensitization: prevalence and impact of the BRCA 1/2 mutation. J Allergy Clin Immunol Pract. 2017;5(3):816–8. https://doi.org/10.1016/j.jaip.2016.08.012.

    Article  PubMed  Google Scholar 

  104. Moon DH, Lee JM, Noonan AM, Annunziata CM, Minasian L, Houston N, et al. Deleterious BRCA1/2 mutation is an independent risk factor for carboplatin hypersensitivity reactions. Br J Cancer. 2013;109(4):1072–8. https://doi.org/10.1038/bjc.2013.389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Rolfe M, Gegeckas C, Turner S, Orr JW Jr. Predictive factors for carboplatin hypersensitivity reactions in gynecologic cancers: effect of BRCA status. J Oncol Pharm Pract. 2020. https://doi.org/10.1177/1078155220967988.

  106. Prieto García A. Pineda de la Losa F. Immunoglobulin E-mediated severe anaphylaxis to paclitaxel. J Investig Allergol Clin Immunol. 2010;20(2):170–1.

    PubMed  Google Scholar 

  107. Françoso A, Simioni P. Immunotherapy for the treatment of colorectal tumors: focus on approved and in-clinical-trial monoclonal antibodies. Drug Des Devel Ther. 2017;11(22):177–84. https://doi.org/10.2147/DDDT.S119036.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Steinke JW, Platts-Mills TA, Commins SP. The alpha-gal story: lessons learned from connecting the dots. J Allergy Clin Immunol Pract. 2015;135(3):589–96. https://doi.org/10.1016/j.jaci.2014.12.1947.

    Article  CAS  Google Scholar 

  109. Wilson JM, Schuyler AJ, Schroeder N, Platts-Mills TA. Galactose-α-1,3-galactose: atypical food allergen or model IgE hypersensitivity? Curr Allergy Asthma Rep. 2017;17(1):8. https://doi.org/10.1007/s11882-017-0672-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Bonomo P, Loi M, Desideri I, Olmetto E, Delli Paoli C, Terziani F, et al. Incidence of skin toxicity in squamous cell carcinoma of the head and neck treated with radiotherapy and cetuximab: a systematic review. Crit Rev Oncol Hematol. 2017;120:98–110. https://doi.org/10.1016/j.critrevonc.2017.10.011.

    Article  PubMed  Google Scholar 

  111. Lacouture ME, Anadkat M, Jatoi A, Garawin T, Bohac C, Mitchell E. Dermatologic toxicity occurring during anti-EGFR monoclonal inhibitor therapy in patients with metastatic colorectal cancer: a systematic review. Clin Colorectal Cancer. 2018;17(2):85–96. https://doi.org/10.1016/j.clcc.2017.12.004.

    Article  PubMed  Google Scholar 

  112. Lax T, Long A, Banerji A. Skin testing in the evaluation and management of carboplatin-related hypersensitivity reactions. J Allergy Clin Immunol Pract. 2015;3(6):856–62. https://doi.org/10.1016/j.jaip.2015.07.003.

    Article  PubMed  Google Scholar 

  113. Vetter MH, Khan A, Backes FJ, Bixel K, Cohn DE, Copeland LJ, et al. Outpatient desensitization of patients with moderate (high-risk) to severe platinum hypersensitivity reactions. Gynecol Oncol. 2019;152(2):316–21. https://doi.org/10.1016/j.ygyno.2018.10.037.

    Article  CAS  PubMed  Google Scholar 

  114. Pérez-Rodríguez E, Martínez-Tadeo JA, Pérez-Rodríguez N, Hernández-Santana G, Callero-Viera A, Rodríguez-Plata E, et al. Outcome of 490 desensitizations to chemotherapy drugs with a rapid one-solution protocol. J Allergy Clin Immunol Pract. 2018;6(5):1621–7. https://doi.org/10.1016/j.jaip.2017.11.033.

    Article  PubMed  Google Scholar 

  115. Mawhirt SL, Fonacier L, Calixte R, Davis-Lorton M, Aquino MR. Skin testing and desensitization outcomes among platinum-sensitive oncology patients. Ann Allergy Asthma Immunol. 2018;120(4):437–9. https://doi.org/10.1016/j.anai.2018.01.008.

    Article  PubMed  Google Scholar 

  116. Kendirlinan R, Gümüşburun R, Çerçi P, Özbek E, Altıner S, Çelebi Sözener Z, et al. Rapid drug desensitization with chemotherapeutics (platins, taxanes, and others): a single-center retrospective study. Int Arch Allergy Immunol. 2019;179(2):114–22. https://doi.org/10.1159/000496745.

    Article  CAS  PubMed  Google Scholar 

  117. Bruchim I, Goldberg A, Fishman A, Confino-Cohen R. Carboplatin hypersensitivity: evaluation and successful desensitization protocol. Immunotherapy. 2014;6(8):905–12. https://doi.org/10.2217/imt.14.71.

    Article  CAS  PubMed  Google Scholar 

  118. Dizon DS, Sabbatini PJ, Aghajanian C, Hensley ML, Spriggs DR. Analysis of patients with epithelial ovarian cancer or fallopian tube carcinoma retreated with cisplatin after the development of a carboplatin allergy. Gynecol Oncol. 2002;84(3):378–82. https://doi.org/10.1006/gyno.2001.6519.

    Article  CAS  PubMed  Google Scholar 

  119. Breslow RG, Caiado J, Castells MC. Acetylsalicylic acid and montelukast block mast cell mediator-related symptoms during rapid desensitization. Ann Allergy Asthma Immunol. 2009;102(2):155–60. https://doi.org/10.1016/S1081-1206(10)60247-5.

    Article  CAS  PubMed  Google Scholar 

  120. Lowe PJ, Tannenbaum S, Gautier A, Jimenez P. Relationship between omalizumab pharmacokinetics, IgE pharmacodynamics and symptoms in patients with severe persistent allergic (IgE-mediated) asthma. Br J Clin Pharmacol. 2009;68:61–76. https://doi.org/10.1111/j.1365-2125.2009.03401.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Stokes JRCT. The use of anti-IgE therapy beyond allergic asthma. J Allergy Clin Immunol Pract. 2015;3(2):162–6.

    Article  Google Scholar 

  122. Ojaimi S, Harnett P, Fulcher DA. Successful carboplatin desensitization by using omalizumab and paradoxical diminution of total IgE levels. J Allergy Clin Immunol Pract. 2014;2(1):105–6. https://doi.org/10.1016/j.jaip.2013.08.009.

    Article  PubMed  Google Scholar 

  123. Cahill KNHP, de Asis M, Castells M. Use of omalizumab to achieve successful desensitization after oxaliplatin anaphylaxis. Journal of Allergy and Clinical Immunology. 2012;129(2):AB103.

    Article  Google Scholar 

  124. Prieto-García A, Noguerado B, Rojas P, Torrado I, Rodríguez-Fernández A, Tornero P. Unexpected anaphylaxis after completing a desensitization protocol to oxaliplatin: successful adjuvant use of omalizumab. J Investig Allergol Clin Immunol. 2019;29(1):53–5. https://doi.org/10.18176/jiaci.0326.

    Article  CAS  PubMed  Google Scholar 

  125. Gastaminza G, de la Borbolla JM, Goikoetxea MJ, Escudero R, Anton J, Espinos J, et al. A new rapid desensitization protocol for chemotherapy agents. J Investig Allergol Clin Immunol. 2011;21(2):108–12.

    CAS  PubMed  Google Scholar 

  126. Chung SJ, Kang S, Kang RY, Kim YC, Lee KH, Kim TY, et al. A new non-dilution rapid desensitization protocol successfully applied to all-grade platinum hypersensitivity. Cancer Chemother Pharmacol. 2018;82(5):777–85. https://doi.org/10.1007/s00280-018-3662-0.

    Article  CAS  PubMed  Google Scholar 

  127. Vidal C, Méndez-Brea P, López-Freire S, Bernárdez B, Lamas MJ, Armisén M, et al. A modified protocol for rapid desensitization to chemotherapy agents. J Allergy Clin Immunol Pract. 2016;4(5):1003–5. https://doi.org/10.1016/j.jaip.2016.05.015.

    Article  PubMed  Google Scholar 

  128. Li Q, Cohn D, Waller A, Backes F, Copeland L, Fowler J, et al. Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin. Gynecol Oncol. 2014;135(1):90–4. https://doi.org/10.1016/j.ygyno.2014.07.104.

    Article  CAS  PubMed  Google Scholar 

  129. Altwerger G, Florsheim EB, Menderes G, Black J, Schwab C, Gressel GM, et al. Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer. J Cancer Res Clin Oncol. 2018;144(12):2449–56. https://doi.org/10.1007/s00432-018-2753-yThis paper supports the great outcomes of drug desensitization to carboplatin.

  130. Berges-Gimeno MP, Carpio-Escalona LV, Longo-Muñoz F, Bernal-Rubio L, Lopez-Gonzalez P, Gehlhaar P, et al. Does rapid drug desensitization to chemotherapy affect survival outcomes? J Investig Allergol Clin Immunol. 2019;12(0). https://doi.org/10.18176/jiaci.0425.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joana Caiado.

Ethics declarations

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Anaphylaxis and Drug Allergy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Caiado, J., Castells, M.C. Drug Desensitizations for Chemotherapy: Safety and Efficacy in Preventing Anaphylaxis. Curr Allergy Asthma Rep 21, 37 (2021). https://doi.org/10.1007/s11882-021-01014-x

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11882-021-01014-x

Keywords

Navigation