Skip to main content
SpringerLink
Log in

Carboplatin desensitization in the era of target therapies: still worthwhile?

  • Research
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Purpose

Unresectable pediatric low-grade gliomas (LGG) usually need adjuvant therapy, and carboplatin hypersensitivity reaction (HR) commonly leads to premature treatment cessation of a standard chemotherapy regimen. In the molecular era, advances in understanding tumor genetic characteristics allowed the development of targeted therapies for this group of tumors; however, cost-effectiveness assessment of treatments, especially in low-income countries, is crucial. The aim is to describe the results of carboplatin desensitization protocol in a single center in a middle-income country.

Method

Prospective analysis of children with LGG submitted to carboplatin desensitization from December 2017 to June 2020 with follow-up until April 2024.

Results

Nine patients were included. The mean age was 11 years. Five patients were male. Seven had optic pathway and two cervicomedullary location. Six had histologic diagnosis and four molecular analyses. The incidence of carboplatin reactions during the study period was 39.1%. Six patients underwent skin prick test, three with positive results. The first HR occurred, on average, around the 9th cycle of treatment. All patients had cutaneous symptoms, and five out of nine had anaphylaxis as the first reaction. 77.7% of the patients completed the protocol, and the clinical benefit rate (stable disease and partial response) was 88.8%. Six patients further required other lines of therapy. Monthly, the total cost for carboplatin was $409.09, and for target therapies (dabrafenib plus trametinib), $4929.28 to $5548.57.

Conclusion

Our study presented an interesting and cost-effective option where desensitization allowed children with HR to be treated with first-line therapy, avoiding the discontinuation of an effective treatment.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data Availability

No datasets were generated or analyzed during the current study.

References

  1. Manoharan N, Liu KX, Mueller S, Haas-Kogan DA, Bandopadhayay P (2023) Pediatric low-grade glioma: targeted therapeutics and clinical trials in the molecular era. Neoplasia 36:100857. https://doi.org/10.1016/j.neo.2022.100857

    Article  CAS  PubMed  Google Scholar 

  2. Ryall S, Tabori U, Hawkins C (2020) Pediatric low-grade glioma in the era of molecular diagnostics. Acta Neuropathol Commun 8(1):30. https://doi.org/10.1186/s40478-020-00902-z

    Article  PubMed  PubMed Central  Google Scholar 

  3. de Blank P, Fouladi M, Huse JT (2020) Molecular markers and targeted therapy in pediatric low-grade glioma. J Neurooncol 150(1):5–15. https://doi.org/10.1007/s11060-020-03529-1

    Article  PubMed  Google Scholar 

  4. Manoharan N, Choi J, Chordas C, Zimmerman MA, Scully J, Clymer J, Filbin M, Ullrich NJ, Bandopadhayay P, Chi SN, Yeo KK (2020) Trametinib for the treatment of recurrent/progressive pediatric low-grade glioma. J Neurooncol 149(2):253–262. https://doi.org/10.1007/s11060-020-03592-8

    Article  CAS  PubMed  Google Scholar 

  5. Selt F, van Tilburg CM, Bison B, Sievers P, Harting I, Ecker J, Pajtler KW, Sahm F, Bahr A, Simon M, Jones DTW, Well L, Mautner VF, Capper D, Hernáiz Driever P, Gnekow A, Pfister SM, Witt O, Milde T (2020) Response to trametinib treatment in progressive pediatric low-grade glioma patients. J Neurooncol 149(3):499–510. https://doi.org/10.1007/s11060-020-03640-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Packer RJ, Lange B, Ater J, Nicholson HS, Allen J, Walker R, Prados M, Jakacki R, Reaman G, Needles MN et al (1993) Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol 11(5):850–856. https://doi.org/10.1200/JCO.1993.11.5.850

    Article  CAS  PubMed  Google Scholar 

  7. Tsuchida Y, Therasse P (2001) Response evaluation criteria in solid tumors (RECIST): new guidelines. Med Pediatr Oncol 37(1):1–3. https://doi.org/10.1002/mpo.1154

    Article  CAS  PubMed  Google Scholar 

  8. Brown SGA (2004) Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 114(371):376

    Google Scholar 

  9. Otani IM, Wong J, Banerji A (2017) Platinum chemotherapy hypersensitivity. Immunol Allergy Clin North Am 37(4):663–677

    Article  PubMed  Google Scholar 

  10. Cappellano AM, Petrilli AS, da Silva NS, Silva FA, Paiva PM, Cavalheiro S, Bouffet E (2015) Single agent vinorelbine in pediatric patients with progressive optic pathway glioma. J Neurooncol 121(2):405–412. https://doi.org/10.1007/s11060-014-1652-6

    Article  CAS  PubMed  Google Scholar 

  11. Dassi N, Silva NS, Silva FA, Almeida DB, Oliveira MR, Cavalheiro S, Dastoli PA, Seixas MT, Cappellano AM (2021) Single-agent oral vinorelbine in the treatment of pediatric progressive optic pathway glioma: a single institutional experience. Clin Oncol Res 2613–4942 https://doi.org/10.31487/j.COR.2021.07.05

  12. Lassaletta A, Scheinemann K, Zelcer SM, Hukin J, Wilson BA, Jabado N, Carret AS, Lafay-Cousin L, Larouche V, Hawkins CE, Pond GR, Poskitt K, Keene D, Johnston DL, Eisenstat DD, Krishnatry R, Mistry M, Arnoldo A, Ramaswamy V, Huang A, Bartels U, Tabori U, Bouffet E (2016) Phase II weekly vinblastine for chemotherapy-naïve children with progressive low-grade glioma: a Canadian Pediatric Brain Tumor Consortium Study. J Clin Oncol 34(29):3537–3543. https://doi.org/10.1200/JCO.2016.68.1585

    Article  CAS  PubMed  Google Scholar 

  13. Lee CW, 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 95:370–376

    Article  CAS  PubMed  Google Scholar 

  14. Ruggiero A, Rizzo D, Catalano M, Maurizi P, Mastrangelo S, Attinà G, Riccardi R (2017) Rechallenge to carboplatin in children with low grade glioma and carboplatin hypersensitivity reactions. Front Pharmacol 7(8):179. https://doi.org/10.3389/fphar.2017.00179

    Article  CAS  Google Scholar 

  15. Genc DB, Canpolat C, Berrak SG (2012) Clinical features and management of carboplatin-related hypersensitivity reactions in pediatric low-grade glioma. Support Care Cancer 20:385–393

    Article  PubMed  Google Scholar 

  16. Lafay-Cousin L, Sung L, Carret AS, Hukin J, Wilson B, Johnston DL, Zelcer S, Silva M, Odame I, Mpofu C, Strother D, Bouffet E (2008) Carboplatin hypersensitivity reaction in pediatric patients with low-grade glioma: a Canadian Pediatric Brain Tumor Consortium experience. Cancer 112:892–899

    Article  CAS  PubMed  Google Scholar 

  17. Shah AC, Minturn JE, Li Y, Belasco JB, Phillips PC, Kang TI, Cole KA, Waanders AJ, Pollack R, Didomenico C, Wildes C, Fisher MJ (2015) Carboplatin rechallenge after hypersensitivity reactions in pediatric patients with low-grade glioma. Pediatr Blood Cancer 9999:1–6

    Google Scholar 

  18. Gnekow AK, Falkenstein F, von Hornstein S, Zwiener I, Berkefeld S, Bison B, Warmuth-Metz M, Driever PH, Soerensen N, Kortmann RD, Pietsch T, Faldum A (2012) Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low-grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology. Neuro Oncol 14:1265–1284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI et al (2008) Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol 122(3):574–580

    Article  CAS  PubMed  Google Scholar 

  20. Macy E, Ensina LF (2019) Controversies in allergy: is skin testing required prior to drug challenges? J Allergy Clin Immunol Pract 7:412–417

    Article  PubMed  Google Scholar 

  21. 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  PubMed  Google Scholar 

  22. Silver J, Garcia-Neuer M, Lynch D-M, Pasaoglu G, Sloane DE, Castells M (2020) Endophenotyping oxaliplatin hypersensitivity: personalizing desensitization to the atypical platin. J Allergy Clin Immunol: In Practice 8(5):1668-1680.e2

    Google Scholar 

  23. Cernadas JR (2017) Reactions to cytostatic agents in children. Curr Opin Allergy Clin Immunol 17(4):255–261

    Article  CAS  PubMed  Google Scholar 

  24. Scheinemann K, Bartels U, Tsangaris E, Hawkins C, Huang A, Dirks P, Fried I, Bouffet E, Tabori U (2011) Feasibility and efficacy of repeated chemotherapy for progressive pediatric low-grade gliomas. Pediatr Blood Cancer 57(1):84–88. https://doi.org/10.1002/pbc.22917

    Article  PubMed  Google Scholar 

  25. Bailey S, Davidson A, Parkes J, Tabori U, Figaji A, Epari S, Chinnaswamy G, Dias-Coronado R, Casavilca-Zambrano S, Amayiri N, Vassal G, Bouffet E, Clifford SC (2022) How can genomic innovations in pediatric brain tumors transform outcomes in low- and middle-income countries? JCO Glob Oncol 8:e2200156. https://doi.org/10.1200/GO.22.00156

    Article  PubMed  PubMed Central  Google Scholar 

  26. Moreira DC, Lam CG, Bhakta N, Boop FA, Chiang J, Merchant TE, Rodriguez-Galindo C, Gajjar A, Qaddoumi I (2023Apr) Tackling pediatric low-grade gliomas: a global perspective. JCO Glob Oncol 9:e2300017. https://doi.org/10.1200/GO.23.00017

    Article  PubMed  PubMed Central  Google Scholar 

  27. Cernadas J, Vasconcelos MJ, Fernandes AP, Carneiro-Leão L, Gil-da-Costa MJ (2021) Desensitization to carboplatin in low-grade glioma. A revision of 100 treatments in children. Pediatr Allergy Immunol 32(6):1388–1391. https://doi.org/10.1111/pai.13525

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics’ Oncology, IOP-GRAACC-Federal University of Sao Paulo, Sao Paulo, Brazil

    Natália Dassi, Andrea Maria Cappellano, Daniela Barbosa de Almeida & Nasjla Saba da Silva

  2. Department of Pediatrics’ Allergy, Immunology, and Rheumatology- Federal University of Sao Paulo, Sao Paulo, Brazil

    Fernanda Sales da Cunha, Chayanne Andrade de Araujo, Denise Neiva Santos de Aquino & Luis Felipe Chiaverini Ensina

Authors
  1. Natália Dassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fernanda Sales da Cunha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Maria Cappellano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chayanne Andrade de Araujo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Denise Neiva Santos de Aquino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniela Barbosa de Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nasjla Saba da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Luis Felipe Chiaverini Ensina
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by all authors. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Andrea Maria Cappellano.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the hospital’s Research Ethics Board IOP-GRAACC and UNIFESP (Federal University of Sao Paulo).

Consent for publication

The study was approved by the hospital’s Research Ethics Board IOP-GRAACC and UNIFESP (Federal University of Sao Paulo).

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dassi, N., da Cunha, F.S., Cappellano, A.M. et al. Carboplatin desensitization in the era of target therapies: still worthwhile?. Childs Nerv Syst (2024). https://doi.org/10.1007/s00381-024-06564-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00381-024-06564-9

Keywords

Search

Navigation