Skip to main content
Top
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Case report

Relapsing pneumonitis due to two distinct inhibitors of the MAPK/ERK pathway: report of a case

Authors: Violaine Giraud, Christine Longvert, Solène Houlle-Crepin, Claire Danel, Sylvie Labrune, Philippe Camus, Philippe Saiag, Thierry Chinet

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

BRAF and MEK are component of the MAPK/ERK pathway and inhibitors of these proteins have significantly improved the outcome of metastatic melanoma. We report for the first time two sequential episodes of pneumonitis presumably induced by trametinib (a MEK inhibitor) and vemurafenib (a BRAF inhibitor) in a 50 year-old man.

Case presentation

While receiving trametinib for a metastatic melanoma, the patient developed non-febrile acute respiratory failure in the context of bilateral ground-glass opacities and sub pleural reticulations on high resolution computed tomography. An excess of lymphocytes was found in the bronchoalveolar lavage fluid. Outcome was favorable after simple drug discontinuation. He subsequently developed a similar clinical-imaging picture 6 months into vemurafenib. A transthoracic lung biopsy disclosed interstitial lymphocytic infiltrate, poorly-formed granulomas with multinucleated giant cells and scattered eosinophils. Outcome was again favorable after simple drug discontinuation.

Conclusion

These two episodes in the same patient suggest that MAPK/ERK inhibitors may cause interstitial lung disease and may exert cross toxicity. This side effect is of particular interest for physicians in charge of patients with melanoma but this drug family is currently under development for several other solid tumors.
Literature
1.
go back to reference Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.CrossRefPubMedPubMedCentral Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.CrossRefPubMedPubMedCentral
2.
go back to reference Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(28):358–65.CrossRefPubMed Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(28):358–65.CrossRefPubMed
3.
go back to reference Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma. N Engl J Med. 2012;367(2):107–14.CrossRefPubMed Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma. N Engl J Med. 2012;367(2):107–14.CrossRefPubMed
4.
go back to reference Lacasse Y, Girard M, Cormier Y. Recent advances in hypersensitivity pneumonitis. Chest. 2012;142(1):208–17.CrossRefPubMed Lacasse Y, Girard M, Cormier Y. Recent advances in hypersensitivity pneumonitis. Chest. 2012;142(1):208–17.CrossRefPubMed
5.
go back to reference Xu JF, Shen L, Zhang Y, Zhang P, Qu JM, Li HP. Lung biopsy proved hypersensitivity pneumonitis without known offending antigen: characteristics and follow up. Clin Respir J. 2014;8(3):297–304.CrossRefPubMed Xu JF, Shen L, Zhang Y, Zhang P, Qu JM, Li HP. Lung biopsy proved hypersensitivity pneumonitis without known offending antigen: characteristics and follow up. Clin Respir J. 2014;8(3):297–304.CrossRefPubMed
6.
go back to reference Flieder DB, Travis WD. Pathologic characteristics of drug induced lung disease. Cli Chest Med. 2004;25(1):37–45.CrossRef Flieder DB, Travis WD. Pathologic characteristics of drug induced lung disease. Cli Chest Med. 2004;25(1):37–45.CrossRef
7.
go back to reference Myers J, Limper A, Swensen S. Drug-Induced lung disease: a pragmatic classification incorporating HRCT appearance. Sem Respir Crit Care Med. 2003;24(4):445–54.CrossRef Myers J, Limper A, Swensen S. Drug-Induced lung disease: a pragmatic classification incorporating HRCT appearance. Sem Respir Crit Care Med. 2003;24(4):445–54.CrossRef
9.
go back to reference Cleverley J, Screaton N, Hiorns M, Flint J, Muller N. Drug-induced lung disese: high –resolution CT and histologic findings. Clin Radiol. 2002;57:292–9.CrossRefPubMed Cleverley J, Screaton N, Hiorns M, Flint J, Muller N. Drug-induced lung disese: high –resolution CT and histologic findings. Clin Radiol. 2002;57:292–9.CrossRefPubMed
10.
go back to reference Schmitt L, Schumann T, Löser C, Dippel E. Vemurafenib-induced pulmonary injury. Onkologie. 2013;36(11):685–6.CrossRefPubMed Schmitt L, Schumann T, Löser C, Dippel E. Vemurafenib-induced pulmonary injury. Onkologie. 2013;36(11):685–6.CrossRefPubMed
11.
go back to reference Min JH, Lee HY, Lim H, Ahn MJ, Park K, Chung MP, et al. Drug-induced interstitial lung disease in tyrosine kinase inhibitor therapy for non small cell lung cancer: a review on current insight. Cancer Chemother Pharmacol. 2011;68(5):1099–109.CrossRefPubMed Min JH, Lee HY, Lim H, Ahn MJ, Park K, Chung MP, et al. Drug-induced interstitial lung disease in tyrosine kinase inhibitor therapy for non small cell lung cancer: a review on current insight. Cancer Chemother Pharmacol. 2011;68(5):1099–109.CrossRefPubMed
12.
go back to reference Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694–703.CrossRefPubMedPubMedCentral Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694–703.CrossRefPubMedPubMedCentral
Metadata
Title
Relapsing pneumonitis due to two distinct inhibitors of the MAPK/ERK pathway: report of a case
Authors
Violaine Giraud
Christine Longvert
Solène Houlle-Crepin
Claire Danel
Sylvie Labrune
Philippe Camus
Philippe Saiag
Thierry Chinet
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1754-3

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine