Tumoral hemorrhage of brain metastasis from non-small cell lung cancer after gefitinib therapy: two case reports and literature review

Background: Gefitinib is one of small molecule inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR TKIs). Clinical trials have demonstrated that it is effective in the treatment of a subset of patients with advanced non-small cell lung cancer (NSCLC). It has also been regarded as a relatively safe agent, and in addition to a small proportion of fatal interstitial pneumonia, the common adverse drug reactions of gefitinib are diarrhea and skin rash, which are generally mild and reversible. Herein, we report the first two cases of brain hemorrhage that might be involved in the use of gefitinib. Case presentation: In our report, two patients with brain metastasis from NSCLC are described to develop brain hemorrhage after gefitinib therapy. The hemorrhage in one case occurred one month after gefitinib combined with whole brain irradiation (WBRT), and in another case it developed slowly with a brain metastasis 8 months after gefitinib monotherapy for diffuse pulmonary metastasis from a previously operated lung cancer. Conclusion: We speculate brain hemorrhage as possible adverse drug reaction of gefitinib with NSCLC and suggest that the clinicians be aware of this presumably rare entity. More data are needed to confirm our findings, especially when gefitinib is used in settings of brain metastases either from NSCLC or other origins.