Hemorrhage of brain metastasis from non-small cell lung cancer post gefitinib therapy: two case reports and review of the literature

Abstract

Background: Gefitinib is one of the small molecule inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR TKIs). Clinical trials have demonstrated it is effective for treatment of a subset of patients with advanced non-small cell lung cancer (NSCLC). Gefitinib has been generally considered to be a relatively safe agent. Besides a small proportion of fatal interstitial pneumonia, the common adverse drug reactions of gefitinib include diarrhea and skin rash, which are generally mild and reversible. Herein, we report the first two cases of brain metastasis hemorrhage that might be involved with the use of gefitinib.

Case presentation: Two patients with brain metastasis from NSCLC developed brain hemorrhage after gefitinib therapy. The hemorrhage in one case occurred one month after gefitinib combined with whole brain radiation therapy (WBRT), and in the another case hemorrhage developed slowly within brain metastases eight months post gefitinib monotherapy for diffuse pulmonary metastasis from a lung cancer undergone surgical removal previously.

Conclusion: We speculate brain hemorrhage could be one of the adverse drug reactions of gefitinib treatment for NSCLC and suggest clinicians be aware of this possible rare entity. More data are needed to confirm our findings, especially when gefitinib is used in the settings of brain metastases from NSCLC or other origins.

Figure 1

Case 1. A: Prior to gefitinib therapy, chest CT scan shows a primary lesion (arrow) in the upper lobe of right lung and multiple pulmonary metastatic nodules (arrowheads) in both lungs. B: One month later with gefitinib therapy, chest CT scan shows significant shrinkage of the primary lesion (arrow) as well as marked absorption of metastatic nodules.

Figure 2

Case 1. A: Contrast-enhanced T1-weighted brain MRI shows multiple metastatic lesions, with the largest one (arrow) in the left occipital lobe. B: One month later with gefitinib therapy together with two weeks' WBRT, T1-weighted MRI demonstrates a subacute hematoma (arrow) in the metastatic lesion.

Figure 3

Case 2. A: Chest CT scans shows pulmonary metastatic dissemination (arrows) from a previously operated NSCLC in the right lung. A patchy shadow (arrowhead) representing radiation-induced fibrosis is also observed. B: About 2 month later with gefitinib therapy, chest CT scan shows significant absorption of the metastatic lesions.

Figure 4

Case 2. A: T1-weighted brain MRI shows a metastatic lesion of heterogeneous signal intensities in the left thalamus (arrow). Components of hyper-signal intensities represent subacute hemorrhage. B: This lesion is also of heterogeneous signal intensities on T2-weighted images, with components of hypointense hemosiderins representing chronic hemorrhage (arrow). C: Contrast-enhanced MRI shows inhomogeneous enhancement of the lesion (arrow).