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Q. Hong

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    CALC - Chinese Alliance Against Lung Cancer Session (ID 79)

    • Event: WCLC 2013
    • Type: Other Sessions
    • Track: Other Topics
    • Presentations: 1
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      CALC.12 - IPF Caused by EGFR-TKIs in Asia (ID 3879)

      07:30 - 12:00  |  Author(s): Q. Hong

      • Abstract
      • Slides

      Drug-associated interstitial lung disease (ILD) is not uncommon, but it may developed to fatal acute respiratory distress syndrome, so an accurate diagnosis based on clinical, radiological and histological manifestations is important. As an EGFR-TKI, Gefitinib or Erlotinib has been widely used in advanced NSCLC, although it may prolong the patient’s survival, the possibility of ILD associated with EGFR-TKI remains a big problem that we need to confront especially in Asian NSCLC patient. Diagnosis For the assignation of ILD, patient usually need to accord with the following requirements: (1) progressive dyspnea with or without cough or fever, (2) radiographic findings(HRCT recommended) show bilateral, diffuse, or patchy interstitial and/or alveolar opacifications, (3) lack of evidence of infection and progression of underlying lung cancer, (4) consistent pathologic findings if available. Establishing a diagnosis on EGFR-TKI associated ILD is often difficult, and is particularly challenging in a patient having been given chemotherapy and/or radiotherapy, chemotherapy and radiotherapy, either alone or in combination, have been associated with the development of ILD. In addition, infections, and other environmental exposures can also mimic ILD. The characteristic images of EGFR-TKI associated ILD were of patchy diffuse ground-glass shadows; several other characteristic HRCT patterns can also been observed. In acute forms of ILD, ground-glass attenuation is usually seen bilaterally in the lung fields. In chronic forms of the disease, “honeycombing” is seen that results from extensive pulmonary fibrosis and loss of acinar architecture of the lungs. Although ILD can occur during the first 3 months of treatment, the median time to onset was actually 24 to 42 days, and ILD developed in most patients within the first 4 weeks of treatment, with possibly rapid progression.On the other hand, ILD can develop in patients who are retreated with EGFR-TKI after a period of interruption. Therefore, all patients receiving EGFR-TKI who present with an acute onset of dyspnea, regardless of the presence of cough or low-grade fever, should be promptly evaluated, especially during the first month of treatment. Epidemiology There are more frequent reports of EGFR TKI-associated ILD in Japan than elsewhere in the world. The causes for this worldwide differences are unknown and require further scientific investigation. Several reasons have been suggested for this difference, including differences in follow-up period, the clinical characteristics of the study population, and the applied diagnostic criteria for ILD. Pre-existing ILD, including usual interstitial pneumonia, has been found in the reported EGFR-TKI induced ILD patients,the presence of IPF seems to be an important risk factor. Alternatively, there may be a specific increased genetic susceptibility to ILD among the Japanese population. However, this ethnic difference in reporting rates does not extend to other Asian countries, where the frequency of ILD is comparable with the rest of the world Mechanism of ILD The molecular mechanisms leading to ILD are also unclear. The distribution of EGF and EGFR in normal adult human lung has been demonstrated by immunohistochemistry, with expression observed in the basal cell layer of the bronchial epithelium . EGF signaling probably represents an important mechanism that helps coordinate the process of recovery from lung injury by stimulating epithelial repopulation and restoration of barrier integrity. Some investigator have suggested that EGFR-TKI therapy may augment any underlying pulmonary fibrosis via a decrease in EGFR phosphorylation with a coincident decrease in regenerative epithelial proliferation. Therefore, it is possible that EGFR inhibition will at least in part reduce the ability of pneumocytes to respond to lung injury. Compared with other EGFR inhibitors, the largest amount of information regarding the association with ILD is available for gefitinib, as this agent has been given to more patients than any other EGFR-TKIs. Treatment Treatment of EGFR TKI–induced ILD include supplemental oxygen, empirical antibiotics, and mechanical ventilation depending on the severity of the situation. Immediate discontinuation of the TKI drug is recommended . Acute pneumonitis commonly resolves on discontinuation of therapy, although in severe cases patients , systemic corticosteroids are usually prescribed, Prognosis with treatment is good if the diagnosis is made early; however, once fibrosis has occurred, the damage may be permanent with irreversible loss of lung function.

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