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EDITORIAL
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 1
 

Tuberculosis in epidermal growth factor receptor mutation in lung adenocarcinoma on treatment with gefitinib/erlotinib


Department of Pulmonary Medicine, ESI-PGIMSR, New Delhi, India

Date of Web Publication1-Dec-2017

Correspondence Address:
Dr. D Gothi
Department of Pulmonary Medicine, ESI-PGIMSR, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_503_16

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How to cite this article:
Gothi D, Spalgais S. Tuberculosis in epidermal growth factor receptor mutation in lung adenocarcinoma on treatment with gefitinib/erlotinib. Indian J Cancer 2017;54:1

How to cite this URL:
Gothi D, Spalgais S. Tuberculosis in epidermal growth factor receptor mutation in lung adenocarcinoma on treatment with gefitinib/erlotinib. Indian J Cancer [serial online] 2017 [cited 2017 Dec 11];54:1. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/1/219589


Tuberculosis (TB) is known to occur in bronchogenic carcinoma. We analyzed cancer registry of Department of Pulmonary Medicine from January 2015 to December 2015. There were 25 cases of lung cancer of which 14 had adenocarcinoma, 7 of them were epidermal growth factor receptor (EGFR) gene mutation positive. Of these seven cases, three patients developed TB. No other case developed TB.

Three adenocarcinoma cases that developed TB were a 42-year-old nonsmoker female, a 65-year-old chronic smoker male, and a 72-year-old nonsmoker female. Two of them had Stage IV and one had Stage IIIB disease. All the three cases had EGFR mutation positive. One of the patients had histopathologically proven tuberculous pleural effusion while the other two had smear-positive pulmonary TB. All the three patients were on gefitinib or erlotinib for more than 2 months. After the diagnosis of TB, tyrosine kinase inhibitors (TKIs) were continued. Anti-TB treatment (ATT) was given without rifampicin, i.e. streptomycin/isoniazid/ethambutol/pyrazinamide for 2 months followed by isoniazid and ethambutol for 7 months. Both the females received only TKI, but the male had received radiotherapy and chemotherapy as well. Both the females improved on the treatment. Chest radiographs of patients who improved on treatment are shown in [Figure 1] and [Figure 2].
Figure 1: Chest radiograph of case 1: (a) Right upper and mid-zone heterogeneous opacity at the time of diagnosis of carcinoma lung. (b) Decreased mass lesion with treatment. (c) Left-side pleural effusion after 8-month treatment of tyrosine kinase inhibitors. (d) Resolution of pleural effusion with antituberculous treatment

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Figure 2: Chest radiograph of case 3: (a) Left parahilar heterogeneous opacity at diagnosis of carcinoma lung. (b) Decreased mass lesion with treatment after 6 months of tyrosine kinase inhibitors. (c) Bilateral nonhomogeneous opacities more on the left side at the diagnosis of pulmonary tuberculosis. (d) Decreased lung opacities on both sides after with antituberculous treatment

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The EGFR belongs to the ErbB family of transmembrane tyrosine kinase receptors.[1] Epiregulin, a 46-amino acid protein that belongs to the EGF family of peptide hormones, binds with EGFR (EGFR/ErbB1) and ErbB4 (human epidermal growth factor receptor [HER] 4). This epiregulin can stimulate signaling of ErbB2 (HER2/Neu) and ErbB3 (HER3). Polymorphisms in the epiregulin gene are associated with increased susceptibility to Mycobacterium tuberculosis infections.[2] Hence, it is possible that TB in our patients was due to EGFR mutation.

Tumor necrosis factor (TNF) is critical for maintaining the latency of tuberculous infection. Erlotinib and gefitinib appear to have a secondary mechanism of action as TNF-α inhibitors.[3] Imatinib, another TKI, has been reported to increases susceptibility to TB.[4] Hence, another possibility is that these patients had TB due to gefitinib or erlotinib.

Co-administration of rifampicin with erlotinib/gefitinib/afatinib decreases the plasma concentrations and the efficacy of TKIs. There is no published data on their co-administration, though rifampicin may be given with TKI after increasing TKI dose with close drug monitoring.[1] However, when TKI drug monitoring is not available, ATT may be given without rifampicin for 9 months. Two of our cases responded to treatment while the third one expired due to progression of malignancy.

 
  References Top

1.
Peters S, Zimmermann S, Adjei AA. Oral epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: comparative pharmacokinetics and drug-drug interactions. Cancer Treat Rev 2014;40:917-26.  Back to cited text no. 1
[PUBMED]    
2.
Riese DJ 2nd, Cullum RL. Epiregulin: Roles in normal physiology and cancer. Semin Cell Dev Biol 2014;28:49-56.  Back to cited text no. 2
    
3.
Ueno Y, Sakurai H, Matsuo M, Choo MK, Koizumi K, Saiki I. Selective inhibition of TNF-alpha-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib. Br J Cancer 2005;92:1690-5.  Back to cited text no. 3
[PUBMED]    
4.
Daniels JM, Vonk-Noordegraaf A, Janssen JJ, Postmus PE, van Altena R. Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia. Eur Respir J 2009;33:670-2.  Back to cited text no. 4
[PUBMED]    


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