Submit Your Article CMED MEACR meeting
Home Print this page Email this page Users Online: 816
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
CASE REPORT
Year : 2012  |  Volume : 1  |  Issue : 4  |  Page : 242-244

Trastuzumab-induced pulmonaryfibrosis: A case report and review of literature


1 Department of Radiotherapy, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Pulmonary Medicine, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication21-Jan-2013

Correspondence Address:
Tamojit Chaudhuri
Department of Radiotherapy, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-0513.106281

Rights and Permissions
  Abstract 

Optimal treatment for human epidermal growth factor receptor 2 (HER2)/neu-positive, node-positive early breast cancer should include the monoclonal antibody trastuzumab. This relatively new targeted agent has shown very limited pulmonary toxicity. We report a case of Trastuzumab-induced pulmonary fibrosis in a 41-year-old female that occurred 4 months after starting adjuvant trastuzumab. To the best of our knowledge, this is the first ever report of trastuzumab-induced pulmonary fibrosis in the world of medical literature.

Keywords: Breast cancer,pulmonary fibrosis, trastuzumab


How to cite this article:
Chaudhuri T, Karmakar S. Trastuzumab-induced pulmonaryfibrosis: A case report and review of literature. Clin Cancer Investig J 2012;1:242-4

How to cite this URL:
Chaudhuri T, Karmakar S. Trastuzumab-induced pulmonaryfibrosis: A case report and review of literature. Clin Cancer Investig J [serial online] 2012 [cited 2019 Oct 23];1:242-4. Available from: http://www.ccij-online.org/text.asp?2012/1/4/242/106281


  Introduction Top


The human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20-25% of human breast cancers and is an independent adverse prognostic factor. Trastuzumab is a humanized monoclonal antibody that selectively binds to the extracellular domain of the HER2/neu growth factor receptor. It is indicated for the treatment of metastatic breast cancer with overexpression of HER2 protein, as well as for the adjuvant therapy of node-positive, HER2/neu overexpressing breast cancer along with other chemotherapeutic drugs. While cardiotoxicity of trastuzumab is well recognized, particularly when it is used in combination with anthracyclins, unusual pulmonary toxicities are now becoming apparent.


  Case Report Top


A 41-year-old female, who was a diagnosed case of carcinoma of right breast and had already undergone modified radical mastectomy and axillary dissection, was referred to our department for adjuvant chemoradiation. She had a pT3N1M0, grade III, ER-negative/PR-negative/HER2/neu-positive, intraductal carcinoma. After receiving four cycles of AC chemotherapy (doxorubicin 60 mg/m 2 iv on day 1, cyclophosphamide 600 mg/m 2 iv on day 1, every 2 weekly), she was given adjuvant external beam radiation (50 Gy/25fr) to right chest wall and supraclavicular fossa. She tolerated radiation well, and 2 weeks after completion of radiotherapy, paclitaxel chemotherapy (175 mg/m 2 iv on day 1, every 3 weekly forfour cycles) was started. Due to some logistic and economic issues, she could not afford trastuzumab along with paclitaxel, and the first cycle of trastuzumab (8 mg/kg iv on day 1) was given 2 weeks after the last dose of paclitaxel. After that she received five more cycles of trastuzumab (6 mg/kg iv, every 3 weekly). One week after the sixth cycle of trastuzumab, she presented with complaints of dyspnea and dry cough. On clinical examination, she was afebrile with increased respiratory rate (28/minute). Bilateral wheezing was present on chest auscultation. Her SpO 2 was 87% on room air. Chest X-ray showed ground-glass opacification of the lungs. Routine hematological and biochemical parameters were within normal range, echocardiography was normal. Spirometry yielded the following results: forced expiratory volume in 1 second (FEV1) 48.7% and forced vital capacity (FVC) 42.7%. After admission, she was treated with moist O 2 inhalation (4 liters/hour), intravenous antibiotics and bronchodilators in propped up position. Spiral computed tomography (CT) thorax showed diffuse extensive ground glass attenuation, which was more prominent in the subpleural region, intermixed with interlobular septal thickenings, without any pleuro-pericardial effusion. These findings were suggestive of diffuse alveolar damage or acute phases of interstitial lung disease [Figure 1]. Bronchoscopic lung biopsy revealed interstitial widening with moderate interstitial chronic inflammatory infiltrate composed of lymphocytes and histiocytes along with intraalveolar fibroblastic plugs [Figure 2]. Both blood and urine cultures were negative. As no other underlying cause of dyspnea could be identified, the patient was diagnosed as a case of trastuzumab-induced interstitial fibrosis. Antibiotics were withdrawn and prednisone 40 mg orally once daily was started. After 2 weeks of steroid therapy, her symptoms improved a lot and she was discharged without any need for O 2 inhalation, with gradual tapering dose of prednisolone over 4 weeks. No more cycle of trastuzumab was given thereafter.
Figure 1: HR-CT thorax showing diffuse extensive ground glass attenuation, intermixed with interlobular septalthickenings, suggesting diffuse alveolar damage

Click here to view
Figure 2: Photomicrograph of bronchoscopic lung biopsy showing interstitial widening with moderate interstitial chronic inflammatory infiltrate composed of lymphocytes and histiocytes along with intraalveolar fibroblastic plugs (H and E, ×100)

Click here to view



  Discussion Top


Trastuzumab has become the standard of care in the management of (HER2)-over expressing breast cancers, both in the metastatic and adjuvant setting. Emerging data has shown continued efficacy of the drug even after disease progression in combination with chemotherapy.

Trastuzumab has been well tolerated in several series, and its addition to chemotherapy does not significantly increase the frequency of side effects. [1] The incidence of trastuzumab-induced pneumonitis is 0.4-0.6%, with 0.1% mortality. Trastuzumab-induced pneumonitis may present with rapidly progressive pulmonary infiltrates and respiratory failure after receiving 1 dose of trastuzumab or after 6 weeks of therapy. [2],[3] Acute neutrophilicalveolitis and organizing pneumonia after trastuzumab treatment also have been reported. [4] Infusion-related events, including hypotension, angioedema, bronchospasm, dyspnea, fever, chills, and urticaria has been reported to occur in about 15% of patients. But they are rarely severe, and more common during the first administration of the drug. [5],[6],[7] In a retrospective analysis of the safety of herceptin immunotherapy in metastatic breast cancer, trastuzumab was administered to 25,000 patients, and the only respiratory-associated serious adverse event was infusion-related bronchospasm, which usually occurred within 2.5 h of administration. [8] Severe episodes of hypotension, bronchospasm, and hypoxemia leading to death are rare. [9]

Paclitaxel is also known to cause pneumonitis with estimated frequencies of 0.73-12%. Dyspnea, cough, hypoxemia, and pulmonary infiltrates usually develop 1 week to 3 months after treatment. [10],[11],[12] Hypersensitivity reactions are well-recognized complications ofpaclitaxel therapy and typically occur with the first or second dose. [10]

Our patient's symptoms appeared much later than what has been reported in the literature for trastuzumab and paclitaxel separately. Although there is no clear diagnostic test to confirm the actual offensive drug of pulmonary fibrosis in this case, but in view of the fact that the patient became symptomatic during trastuzumabmonotherapy, 4 months after starting therapy, trastuzumab might be the probable cause of lung injury in this patient.


  Conclusion Top


We report an extremely rare case of trastuzumab-induced pulmonary fibrosis in a 41-year-old female that occurred 4 months after starting adjuvant trastuzumab. To the best of our knowledge, this is the first ever report of trastuzumab-induced pulmonary fibrosis in the world of medical literature. Although pulmonary toxicity is unusual with trastuzumab administration, and pulmonary fibrosis is rarer, it is important to be aware of this specific toxicity. Moreover, early recognition andappropriate treatment are of utmost importance to prevent potentially fatal sequelaeof this condition.

 
  References Top

1.Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: The M77001 study group. J Clin Oncol 2005;23:4265-74.  Back to cited text no. 1
[PUBMED]    
2.Vahid B, Mehrotra A. Trastuzumab (Herceptin)-associated lung injury. Respirology 2006;11:655-8.  Back to cited text no. 2
[PUBMED]    
3.Pepels MJ, Boomars KA, van Kimmenade R, Hupperets PS. Life-threatening interstitial lung disease associated with trastuzumab: Case report. Breast Cancer Res Treat 2009;113:609-12.  Back to cited text no. 3
[PUBMED]    
4.Radzikowska E, Szczepulska E, Chabowski M, Bestry I. Organising pneumonia caused by trastuzumab (Herceptin) therapy for breast cancer. Eur Respir J 2003;21:552-5.  Back to cited text no. 4
[PUBMED]    
5.Baselga J, Carbonell X, Castañeda-Soto NJ, Clemens M, Green M, Harvey V, et al. Phase II study of efficacy, safety and pharmacokinetics of trastuzumabmonotherapy administered on a 3-weekly schedule. J Clin Oncol 2005;23:2162-71.  Back to cited text no. 5
    
6.Tripathy D, Slamon DJ, Cobleigh M, Arnold A, Saleh M, Mortimer JE, et al. Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol 2004;22:1063-70.  Back to cited text no. 6
[PUBMED]    
7.Clamon G, Herndon J, Kern J, Govindan R, Garst J, Watson D, et al. Lack of trastuzumab activity in nonsmall cell lung carcinoma with over expression of erb-B2:39810: A phase II trial of Cancer and Leukemia Group B. Cancer 2005;103:1670-5.  Back to cited text no. 7
[PUBMED]    
8.Cook-Bruns N. Retrospective analysis of the safety of Herceptin immunotherapy in metastatic breast cancer. Oncology 2001;61:58-66.  Back to cited text no. 8
[PUBMED]    
9.Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005;353:1673-84.  Back to cited text no. 9
[PUBMED]    
10.Weiss RB, Donehower RC, Wiernik PH, Ohnuma T, Gralla RJ, Trump DL, et al. Hyper sensitivity reactions from taxol. J Clin Oncol 1990;8:1263-8.  Back to cited text no. 10
[PUBMED]    
11.Suzaki N, Hiraki A, Takigawa N, Ueoka H, Tanimoto Y, Kozuki T, et al. Severe interstitial pneumonia induced by paclitaxel in a patient with adenocarcinoma of the lung. Acta Med Okayama 2006;60:295-8.  Back to cited text no. 11
[PUBMED]    
12.Ramanathan R, Reddy VV, Holbert JM, Belani CP. Pulmonary infiltrates following administration of paclitaxel. Chest 1996;110:289-92.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2]


This article has been cited by
1 Application of hypersensitivity skin testing in chemotherapy-induced pneumonitis
James C Kuo,Carolyn A Hawkins,Desmond Yip
Asia Pacific Allergy. 2015; 5(4): 234
[Pubmed] | [DOI]
2 Trastuzumab
Reactions Weekly. 2013; 1443(1): 36
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conclusion
References
Article Figures

 Article Access Statistics
    Viewed3304    
    Printed94    
    Emailed0    
    PDF Downloaded139    
    Comments [Add]    
    Cited by others 2    

Recommend this journal