Skip to main content

Advertisement

SpringerLink
Log in

A new non-dilution rapid desensitization protocol successfully applied to all-grade platinum hypersensitivity

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Desensitization is a safe alternative for patients with hypersensitivity reactions (HSRs) to platinum-based chemotherapeutic agents and widely used in real practice by employing stepwise administration of multiple serial dilutions of the culprit drugs. However, its labor-intensive nature has required a simpler protocol that is easier to prepare and perform.

Methods

We performed an observational study of patients with platinum HSR who underwent a new non-dilution one-bag desensitization protocol. Premedication consisted of Montelukast as well as H1 and H2 blockers. The outcomes and safety profiles of a new protocol were assessed.

Results

A total of 36 patients were recruited (oxaliplatin 23, carboplatin 9, and cisplatin 4) and the most common grade of HSR presented was grade 2 (61.1%), followed by grade 3 (25%), and grade 1 (13.9%). Of 175 desensitization procedures, all cases were successfully completed in re-administration of culprit chemotherapeutic platinum agents; 146 (83.4%) had no breakthrough reactions (BTRs) while 29 (16.6%) did. Most BTRs were mild reactions (grade 1, 51.7%) or moderate reactions (grade 2, 44.8%) of Brown’s Scale. Although there was one case of asymptomatic mild hypotension (grade 3, 3.5%), categorized as severe reaction, dyspnea, desaturation, and anaphylaxis did not occur. The proportion of severe HSRs was significantly lower than that of initial HSRs (3.5% vs. 25%, P = 0.0167).

Conclusions

The new non-dilution desensitization protocol was safe and effective for re-administration of culprit platinum agents in patients with a history of HSRs. Therefore, this new protocol can be used as an alternative to existing protocols using multiple serial dilutions.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AUC:

Area under the curve

BTR:

Breakthrough reaction

HSR:

Hypersensitivity reaction

References

  1. Dasari S, Tchounwou PB (2014) Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 740:364–378

    Article  CAS  Google Scholar 

  2. Kelland L (2007) The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 7(8):573

    Article  CAS  Google Scholar 

  3. Miyamoto S, Okada R, Ando K (2015) Platinum hypersensitivity and desensitization. Jpn J Clin Oncol 45(9):795–804

    Article  Google Scholar 

  4. Caiado J, Picard M (2014) Diagnostic tools for hypersensitivity to platinum drugs and taxanes: skin testing, specific IgE, and mast cell/basophil mediators. Curr Allergy Asthma Rep 14(8):1–12

    Article  CAS  Google Scholar 

  5. Sliesoraitis S, Chikhale P (2005) Carboplatin hypersensitivity. Int J Gynecol Cancer 15(1):13–18

    Article  CAS  Google Scholar 

  6. Comella P, Casaretti R, Sandomenico C, Avallone A, Franco L (2009) Role of oxaliplatin in the treatment of colorectal cancer. Therap Clin Risk Manag 5:229

    Article  Google Scholar 

  7. Markman M, Bookman MA (2000) Second-line treatment of ovarian cancer. The Oncologist 5(1):26–35

    Article  CAS  Google Scholar 

  8. Network NCC (2017) NCCN clinical practice guidelines in oncology-ovarian cancer including fallopian tube cancer and primary peritoneal cancer (Version 2.2017)

  9. Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI, Laidlaw TM, Legere HJ, Nallamshetty SN, Palis RI (2008) Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol 122(3):574–580

    Article  CAS  Google Scholar 

  10. Li Q, Cohn D, Waller A, Backes F, Copeland L, Fowler J, Salani R, O’Malley D (2014) Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin. Gynecol Oncol 135(1):90–94

    Article  CAS  Google Scholar 

  11. Brown SG (2004) Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 114(2):371–376

    Article  Google Scholar 

  12. Lee C-W, Matulonis UA, Castells MC (2005) Rapid inpatient/outpatient desensitization for chemotherapy hypersensitivity: standard protocol effective in 57 patients for 255 courses. Gynecol Oncol 99(2):393–399

    Article  Google Scholar 

  13. Hesterberg PE, Banerji A, Oren E, Penson RT, Krasner CN, Seiden MV, Wong JT (2009) Risk stratification for desensitization of patients with carboplatin hypersensitivity: clinical presentation and management. J Allergy Clin Immunol 123(6):1262–1267. e1261

    Article  CAS  Google Scholar 

  14. Madrigal-Burgaleta R, Berges-Gimeno M, Angel-Pereira D, Ferreiro-Monteagudo R, Guillen-Ponce C, Pueyo C, Gomez de Salazar E, Alvarez-Cuesta E (2013) Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment. Allergy 68(7):853–861

    Article  CAS  Google Scholar 

  15. Wong JT, Ling M, Patil S, Banerji A, Long A (2014) Oxaliplatin hypersensitivity: evaluation, implications of skin testing, and desensitization. J Allergy Clin Immunol Pract 2(1):40–45

    Article  Google Scholar 

  16. Nozawa H, Muto Y, Yamada Y (2008) Desensitization to oxaliplatin with two stages of premedication in a patient with metastatic rectal cancer. Clin Therap 30(6):1160–1165

    Article  CAS  Google Scholar 

  17. Park H, Lee J, Kim S, Kim S, Park K, Lee C, Kang B, Beom S, Shin S, Jung M (2016) A new practical desensitization protocol for oxaliplatin-induced immediate hypersensitivity reactions: a necessary and useful approach. J Investig Allergol Clin Immunol 26(3):168–176

    Article  CAS  Google Scholar 

  18. Confino-Cohen R, Fishman A, Altaras M, Goldberg A (2005) Successful carboplatin desensitization in patients with proven carboplatin allergy. Cancer 104(3):640–643

    Article  CAS  Google Scholar 

  19. Cortijo-Cascajares S, Nacle-López I, García-Escobar I, Aguilella-Vizcaíno MJ, Herreros-de-Tejada A, Castro HC-F, Calleja-Hernández M-Á (2013) Effectiveness of oxaliplatin desensitization protocols. Clin Transl Oncol 15(3):219–225

    Article  CAS  Google Scholar 

  20. Takase N, Matsumoto K, Onoe T, Kitao A, Tanioka M, Kikukawa Y, Yamaguchi S, Fujiwara K, Negoro S (2015) 4-Step 4-h carboplatin desensitization protocol for patients with gynecological malignancies showing platinum hypersensitivity: a retrospective study. Int J Clin Oncol 20(3):566–573

    Article  CAS  Google Scholar 

  21. Okayama T, Ishikawa T, Sugatani K, Yoshida N, Kokura S, Matsuda K, Tsukamoto S, Ihara N, Kuriu Y, Nakanishi M (2015) Hypersensitivity reactions to oxaliplatin: identifying the risk factors and judging the efficacy of a desensitization protocol. Clin Therap 37(6):1259–1269

    Article  CAS  Google Scholar 

  22. Altwerger G, Gressel GM, English DP, Nelson WK, Carusillo N, Silasi D-A, Azodi M, Santin A, Schwartz PE, Ratner ES (2017) Platinum desensitization in patients with carboplatin hypersensitivity: a single-institution retrospective study. Gynecol Oncol 144(1):77–82

    Article  CAS  Google Scholar 

  23. Robinson JB, Singh D, Bodurka-Bevers DC, Wharton JT, Gershenson DM, Wolf JK (2001) Hypersensitivity reactions and the utility of oral and intravenous desensitization in patients with gynecologic malignancies. Gynecol Oncol 82(3):550–558

    Article  CAS  Google Scholar 

  24. Maindrault-Goebel F, André T, Tournigand C, Louvet C, Perez-Staub N, Zeghib N, De Gramont A (2005) Allergic-type reactions to oxaliplatin: retrospective analysis of 42 patients. Eur J Cancer 41(15):2262–2267

    Article  CAS  Google Scholar 

  25. Lee S-Y, Kang H-R, Song W-J, Lee K-H, Han S-W, Cho SH (2014) Overcoming oxaliplatin hypersensitivity: different strategies are needed according to the severity and previous exposure. Cancer Chemother Pharmacol 73(5):1021–1029

    Article  CAS  Google Scholar 

  26. Sohn K-H, Kang D-Y, Kim J-Y, Lee S-Y, Lee K-H, Han S-W, Kang H-R (2018) Incidence and risk of oxaliplatin-induced hypersensitivity in patients with asymptomatic prior exposure: a prospective observational study. J Allergy Clin Immunol Pract. https://doi.org/10.1016/j.jaip.2017.12.026

    Article  PubMed  Google Scholar 

  27. Weiss M, Hug MI, Neff T, Fischer J (2000) Syringe size and flow rate affect drug delivery from syringe pumps. Can J Anesth 47(10):1031–1035

    Article  CAS  Google Scholar 

  28. Weiss M, Bänziger O, Neff T, Fanconi S (2000) Influence of infusion line compliance on drug delivery rate during acute line loop formation. Intensive Care Med 26(6):776–779

    Article  CAS  Google Scholar 

  29. Alvarez-Cuesta E, Madrigal-Burgaleta R, Angel-Pereira D, Ureña-Tavera A, Zamora-Verduga M, Lopez-Gonzalez P, Berges-Gimeno M (2015) Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization. Allergy 70(7):784–794

    Article  CAS  Google Scholar 

  30. Wang AL, Patil SU, Long AA, Banerji A (2015) Risk-stratification protocol for carboplatin and oxaliplatin hypersensitivity: repeat skin testing to identify drug allergy. Ann Allergy Asthma Immunol 115(5):422–428

    Article  CAS  Google Scholar 

  31. Patil SU, Long AA, Ling M, Wilson MT, Hesterberg P, Wong JT, Banerji A (2012) A protocol for risk stratification of patients with carboplatin-induced hypersensitivity reactions. J Allergy Clin Immunol 129(2):443–447

    Article  CAS  Google Scholar 

  32. Leguy-Seguin V, Jolimoy G, Coudert B, Pernot C, Dalac S, Vabres P, Collet E (2007) Diagnostic and predictive value of skin testing in platinum salt hypersensitivity. J Allergy Clin Immunol 119(3):726–730

    Article  CAS  Google Scholar 

  33. Zanotti K, Rybicki L, Kennedy A, Belinson J, Webster K, Kulp B, Peterson G, Markman M (2001) Carboplatin skin testing: a skin-testing protocol for predicting hypersensitivity to carboplatin chemotherapy. J Clin Oncol 19(12):3126–3129

    Article  CAS  Google Scholar 

  34. Lee C-W, Matulonis UA, Castells MC (2004) 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 95(2):370–376

    Article  CAS  Google Scholar 

  35. Garufi C, Cristaudo A, Vanni B, Bria E, Aschelter A, Santucci B, Terzoli E (2003) Skin testing and hypersensitivity reactions to oxaliplatin. Ann Oncol 14(3):497–498

    Article  CAS  Google Scholar 

  36. Markman M, Zanotti K, Kulp B, Peterson G, Markman M (2003) Relationship between a history of systemic allergic reactions and risk of subsequent carboplatin hypersensitivity. Gynecol Oncol 89(3):514–516

    Article  Google Scholar 

  37. Bruchim I, Goldberg A, Fishman A, Confino-Cohen R (2014) Carboplatin hypersensitivity: evaluation and successful desensitization protocol. Immunotherapy 6(8):905–912

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by a Grant from Ministry of Food and Drug Safety to the regional pharmacovigilance center in 2017.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, South Korea

    Soo Jie Chung, Sung-Yoon Kang, Young-Chan Kim, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han & Hye-Ryun Kang

  2. Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, South Korea

    Soo Jie Chung, Sung-Yoon Kang, Young-Chan Kim & Hye-Ryun Kang

  3. Department of Pharmacy, Seoul National University College of Medicine, Seoul, South Korea

    Rae-Young Kang

  4. Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Kyung-Hun Lee, Tae-Yong Kim & Sae-Won Han

  5. Drug Safety Monitoring Center, Seoul National University Hospital, Seoul, South Korea

    Hye-Ryun Kang

Authors
  1. Soo Jie Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sung-Yoon Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rae-Young Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Young-Chan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kyung-Hun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tae-Yong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sae-Won Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hye-Ryun Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hye-Ryun Kang.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 31 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chung, S.J., Kang, SY., Kang, RY. et al. A new non-dilution rapid desensitization protocol successfully applied to all-grade platinum hypersensitivity. Cancer Chemother Pharmacol 82, 777–785 (2018). https://doi.org/10.1007/s00280-018-3662-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-018-3662-0

Keywords

Search

Navigation