The online version of this article (doi:10.1186/1477-7819-10-235) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
YY wrote the manuscript. CWT, MDL and HS participated in the clinical management of the patient. XFF and YHH carried out the pathological examination and gene analysis. SLM was involved in the final editing. All authors approved the final manuscript.
About 20% to 40% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases during the natural course of their disease. The prognosis for such patients is very poor with limited survival. In addition to the standard whole brain radiation therapy (WBRT), some studies have shown that chemotherapy drugs and/or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) can improve the outcome of these patients. Here, we report a stage IIIA patient who developed multiple brain metastases one year after operation. Oral gefitinib with concurrent WBRT were given as first-line therapy. Complete response and a 50-month progression-free survival (PFS) were obtained. Double dosage of gefitinib (500 mg per day) together with pemetrexed were given as the second-line therapy after the patient developed new brain lesions and leptomeningeal metastasis during the maintenance therapy of gefitinib. The PFS for the second-line therapy was six months. In total, the patient obtained an overall survival of 59 months since the first diagnosis of brain metastases. Mutational analysis showed a 15-nucleotide deletion and a missense mutation in exon 19 of the EGFR gene, and a missense mutation at codon 12 of the K-ras gene. These underlying genetic changes might partially explain the long-term survival of this patient after brain metastases when treated with concurrent or sequential therapies of EGFR-TKI, radiotherapy and chemotherapy.
Surmont V, Smit EF, de Jonge M, Aerts JG, Nackaerts K, Vernhout R, Gras J, Van Wijk A, Phernambucq EC, van Meerbeeck JP, Senan S, Kraaij CJ, Chouaki N, Praag J, van Klaveren RJ: Pemetrexed and cisplatin with concurrent radiotherapy for locally advanced non-small cell and limited disease small cell lung cancer: results from 2 phase I studies. Lung Cancer. 2010, 69: 302-306. 10.1016/j.lungcan.2009.12.001. CrossRefPubMed
Kim DY, Lee KW, Yun T, Kim DW, Kim TY, Heo DS, Bang YJ, Kim NK: Efficacy of platinum-based chemotherapy after cranial radiation in patients with brain metastasis from non-small cell lung cancer. Oncol Rep. 2005, 14: 207-211. PubMed
Barlesi F, Gervais R, Lena H, Hureaux J, Berard H, Paillotin D, Bota S, Monnet I, Chajara A, Robinet G: Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07–01). Ann Oncol. 2011, 22: 2466-2470. 10.1093/annonc/mdr003. CrossRefPubMed
Cappuzzo F, Ardizzoni A, Soto-Parra H, Gridelli C, Maione P, Tiseo M, Calandri C, Bartolini S, Santoro A, Crinò L: Epidermal growth factor receptor targeted therapy by ZD1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC). Lung Cancer. 2003, 41: 227-231. 10.1016/S0169-5002(03)00189-2. CrossRefPubMed
Jackman DM, Holmes AJ, Lindeman N, Wen PY, Kesari S, Borras AM, Bailey C, de Jong F, Jänne PA, Johnson BE: Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib. J Clin Oncol. 2006, 24: 4517-4520. 10.1200/JCO.2006.06.6126. CrossRefPubMed
Clarke JL, Pao W, Wu N, Miller VA, Lassman AB: High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer. J Neurooncol. 2010, 99: 283-286. 10.1007/s11060-010-0128-6. PubMedCentralCrossRefPubMed
Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L, Haney J, Witta S, Danenberg K, Domenichini I, Ludovini V, Magrini E, Gregorc V, Doglioni C, Sidoni A, Tonato M, Franklin WA, Crino L, Bunn PA, Varella-Garcia M: Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst. 2005, 97: 643-655. 10.1093/jnci/dji112. CrossRefPubMed
Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II, Fong KM, Lee H, Toyooka S, Shimizu N, Fujisawa T, Feng Z, Roth JA, Herz J, Minna JD, Gazdar AF: Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 2005, 97: 339-346. 10.1093/jnci/dji055. CrossRefPubMed
Takeda M, Okamoto I, Fujita Y, Arao T, Ito H, Fukuoka M, Nishio K, Nakagawa K: De novo resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in EGFR mutation-positive patients with non-small cell lung cancer. J Thorac Oncol. 2010, 5: 399-400. 10.1097/JTO.0b013e3181cee47e. CrossRefPubMed
Linardou H, Dahabreh IJ, Kanaloupiti D, Siannis F, Bafaloukos D, Kosmidis P, Papadimitriou CA, Murray S: Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol. 2008, 9: 962-972. 10.1016/S1470-2045(08)70206-7. CrossRefPubMed
- Activity of pemetrexed and high-dose gefitinib in an EGFR-mutated lung adenocarcinoma with brain and leptomeningeal metastasis after response to gefitinib
- BioMed Central
Neu im Fachgebiet Chirurgie
e.Med Kampagnen-Visual, Mail Icon II