Hemorrhage of Brain Metastasis from Non-small Cell Lung Cancer Post Gefitinib Therapy: Two Case Reports and Review of the Literature

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2010 Feb 23

PMID 20170543

Citations 11

Authors

Dan-Fang Yan

Sen-Xiang Yan

Jing-Song Yang

Yi-Xiang J Wang

Xiao-Li Sun

Xin-Biao Liao

Jun-Qing Liu

Affiliations

Soon will be listed here.

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.

Citing Articles

Contemplation of the Effect of Nivolumab Plus Cabosantinib Therapy on Cerebral Hemorrhage in Patients with Brain Metastasis of Renal Cell Carcinoma: A Case Report.

Sato Y, Kawasaki Y, Satake Y, Shimoda Y, Katayama H, Sato T Case Rep Oncol. 2023; 16(1):1573-1578.

PMID: 38089733 PMC: 10715752. DOI: 10.1159/000533785.

Brain Metastasis Mimicking Glioma on Imaging Appearance During Tyrosine Kinase Inhibitor Administration: A Case Series and Literature Review.

Rai Y, Takami H, Kawaguchi K, Takayanagi S, Tanaka S, Yasunaga Y Cureus. 2023; 15(8):e43591.

PMID: 37719531 PMC: 10503881. DOI: 10.7759/cureus.43591.

Associated Factors of Spontaneous Hemorrhage in Brain Metastases in Patients with Lung Adenocarcinoma.

Kim S, Lee S, Park M, Joo B, Suh S, Ahn S Cancers (Basel). 2023; 15(3).

PMID: 36765577 PMC: 9913139. DOI: 10.3390/cancers15030619.

The biomarkers and potential pathogenesis of lung cancer related cerebral hemorrhage.

Qin K, Chen Y, Long H, Chen J, Wang D, Chen L Medicine (Baltimore). 2019; 98(20):e15693.

PMID: 31096511 PMC: 6531149. DOI: 10.1097/MD.0000000000015693.

Hemorrhage of a pancreatic metastasis from lung adenocarcinoma after osimertinib therapy.

Hayasaka K, Shiono S, Yanagawa N, Yarimizu K, Suzuki K, Endoh M J Thorac Dis. 2018; 10(9):E686-E689.

PMID: 30416817 PMC: 6196163. DOI: 10.21037/jtd.2018.08.108.

References

Luo X, Andres M, Timiryasova T, Fodor I, Slater J, Gridley D . Radiation-enhanced endostatin gene expression and effects of combination treatment. Technol Cancer Res Treat. 2005; 4(2):193-202. DOI: 10.1177/153303460500400208. View

Ieki R, Saitoh E, Hashimoto E, Ohta T, Yuasa K, Iguchi M . [Alveolar hemorrhage as a possible adverse drug reaction by gefitinib (ZD1839, Iressa)]. Gan To Kagaku Ryoho. 2003; 30(7):977-80. View

Stewart J, Cohen E, Licitra L, Van Herpen C, Khorprasert C, Soulieres D . Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected]. J Clin Oncol. 2009; 27(11):1864-71. DOI: 10.1200/JCO.2008.17.0530. View

Johnson D, Fehrenbacher L, Novotny W, Herbst R, Nemunaitis J, Jablons D . Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004; 22(11):2184-91. DOI: 10.1200/JCO.2004.11.022. View

Socinski M, Langer C, Huang J, Kolb M, Compton P, Wang L . Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. J Clin Oncol. 2009; 27(31):5255-61. DOI: 10.1200/JCO.2009.22.0616. View

Huang Y, Liu S, Wang C, Huang M . Exacerbated radiodermatitis and bilateral subdural hemorrhage after whole brain irradiation combined with epidermal growth factor receptor tyrosine kinase inhibitors for brain metastases in lung cancer. Lung Cancer. 2007; 59(3):407-10. DOI: 10.1016/j.lungcan.2007.07.015. View

Thatcher N, Chang A, Parikh P, Pereira J, Ciuleanu T, von Pawel J . Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005; 366(9496):1527-37. DOI: 10.1016/S0140-6736(05)67625-8. View

Ochs J . Rationale and clinical basis for combining gefitinib (IRESSA, ZD1839) with radiation therapy for solid tumors. Int J Radiat Oncol Biol Phys. 2004; 58(3):941-9. DOI: 10.1016/j.ijrobp.2003.09.094. View

Guillamo J, de Bouard S, Valable S, Marteau L, Leuraud P, Marie Y . Molecular mechanisms underlying effects of epidermal growth factor receptor inhibition on invasion, proliferation, and angiogenesis in experimental glioma. Clin Cancer Res. 2009; 15(11):3697-704. DOI: 10.1158/1078-0432.CCR-08-2042. View

10.

Park J, Park B, Kim J, Lee S, Lee S, Kim H . Gefitinib (ZD1839) monotherapy as a salvage regimen for previously treated advanced non-small cell lung cancer. Clin Cancer Res. 2004; 10(13):4383-8. DOI: 10.1158/1078-0432.CCR-04-0189. View

11.

Cohen M, Williams G, Sridhara R, Chen G, Pazdur R . FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist. 2003; 8(4):303-6. DOI: 10.1634/theoncologist.8-4-303. View

12.

Kim J, Kim H, Choi J, Lee K, Shin Y, Ahn B . Bilateral subdural hemorrhage as a possible adverse event of gefitinib in a patient with non-small cell lung cancer. Lung Cancer. 2008; 64(1):121-3. DOI: 10.1016/j.lungcan.2008.10.007. View

13.

Maiuri F, DAndrea F, Gallicchio B, Carandente M . Intracranial hemorrhages in metastatic brain tumors. J Neurosurg Sci. 1985; 29(1):37-41. View

14.

Raben D, Helfrich B . Angiogenesis inhibitors: a rational strategy for radiosensitization in the treatment of non-small-cell lung cancer?. Clin Lung Cancer. 2004; 6(1):48-57. DOI: 10.3816/CLC.2004.n.021. View

15.

Mok T, Wu Y, Thongprasert S, Yang C, Chu D, Saijo N . Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361(10):947-57. DOI: 10.1056/NEJMoa0810699. View

16.

Shepherd F, Pereira J, Ciuleanu T, Tan E, Hirsh V, Thongprasert S . Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353(2):123-32. DOI: 10.1056/NEJMoa050753. View

17.

Ma S, Xu Y, Deng Q, Yu X . Treatment of brain metastasis from non-small cell lung cancer with whole brain radiotherapy and Gefitinib in a Chinese population. Lung Cancer. 2008; 65(2):198-203. DOI: 10.1016/j.lungcan.2008.10.028. View

18.

Bianco C, Tortora G, Bianco R, Caputo R, Veneziani B, Caputo R . Enhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa). Clin Cancer Res. 2002; 8(10):3250-8. View

19.

Raymond E, Faivre S, Armand J . Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs. 2000; 60 Suppl 1:15-23; discussion 41-2. DOI: 10.2165/00003495-200060001-00002. View

20.

Inoue A, Saijo Y, Maemondo M, Gomi K, Tokue Y, Kimura Y . Severe acute interstitial pneumonia and gefitinib. Lancet. 2003; 361(9352):137-9. DOI: 10.1016/S0140-6736(03)12190-3. View