Erlotinib with pemetrexed/cisplatin for patients with EGFR wild-type lung adenocarcinoma with brain metastases

Zhang,Yalei; Yang,Haihong; Yang,Xinyun; Deng,Qiuhua; Zhao,Meilin; Xu,Xin; He,Jianxing

doi:10.3892/mco.2014.256

Erlotinib with pemetrexed/cisplatin for patients with EGFR wild-type lung adenocarcinoma with brain metastases

Authors:
- Yalei Zhang
- Haihong Yang
- Xinyun Yang
- Qiuhua Deng
- Meilin Zhao
- Xin Xu
- Jianxing He
View Affiliations

Affiliations: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China
Published online on: February 11, 2014 https://doi.org/10.3892/mco.2014.256
Pages: 449-453

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer. Recent reports indicated that erlotinib and pemetrexed exerted synergistic effects against lung adenocarcinoma. The available treatment options for lung cancer with brain metastases (BM) are currently limited. In the present study, we investigated the efficacy of the combined administration of erlotinib and pemetrexed in 9 patients with epidermal growth factor receptor (EGFR) wild-type lung adenocarcinoma with BM. Pemetrexed (500 mg/m2) and cisplatin (20 mg/m2) were administered on day 1 and days 1-3, respectively. Erlotinib (150 mg) was administered daily on days 4-20. The 9 patients harbored EGFR wild-type mutation in the primary tumor tissues. With regard to the BM, no patients achieved complete remission, 7 patients exhibited a partial response (PR), 1 had stable disease (SD) and 1 had progressive disease (PD). As regards the extracranial tumors, 3 patients exhibited a PR, 2 had SD, 3 had PD and 1 was not applicable. The performance status and the symptoms improved in 3 patients following treatment. The median progression-free survival for intracranial and extracranial disease control was 179 and 146.5 days, respectively. The median overall survival was 197.4 days. Therefore, erlotinib combined with pemetrexed/cisplatin, was found to be effective in the treatment of patients with EGFR wild-type lung adenocarcinoma.

View Figures

View References

1.	Hazard LJ, Jensen RL and Shrieve DC: Role of stereotactic radiosurgery in the treatment of brain metastases. Am J Clin Oncol. 28:403–410. 2005. View Article : Google Scholar : PubMed/NCBI
2.	Chi A and Komaki R: Treatment of brain metastasis from lung cancer. Cancers (Basel). 2:2100–2137. 2010. View Article : Google Scholar
3.	Kim JE, Lee DH, Choi Y, et al: Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis. Lung Cancer. 65:351–354. 2009. View Article : Google Scholar
4.	Porta R, Sánchez-Torres JM, Paz-Ares L, et al: Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J. 37:624–631. 2011. View Article : Google Scholar : PubMed/NCBI
5.	Hsiao SH, Lin HC, Chou YT, Lin SE, Kuo CC, Yu MC and Chung CL: Impact of epidermal growth factor receptor mutations on intracranial treatment response and survival after brain metastases in lung adenocarcinoma patients. Lung Cancer. 81:455–461. 2013. View Article : Google Scholar
6.	Shih C, Chen VJ, Gossett LS, et al: LY231514, a pyrrolo [2,3-d] pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Res. 57:1116–1123. 1997.
7.	Bailon O, Chouahnia K, Augier A, et al: Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma. Neuro Oncol. 14:491–495. 2012. View Article : Google Scholar : PubMed/NCBI
8.	Sigmond J, Backus HH, Wouters D, Temmink OH, Jansen G and Peters GJ: Induction of resistance to the multitargeted antifolate pemetrexed (ALIMTA) in WiDr human colon cancer cells is associated with thymidylate synthase overexpression. Biochem Pharmacol. 66:431–438. 2003. View Article : Google Scholar
9.	Spicer J and Harper P: Targeted therapies for non-small cell lung cancer. Int J Clin Pract. 59:1055–1062. 2005. View Article : Google Scholar : PubMed/NCBI
10.	Ranson M, Reck M, Anthoney A, et al: Erlotinib in combination with pemetrexed for patients with advanced non-small-cell lung cancer (NSCLC): a phase I dose-finding study. Ann Oncol. 21:2233–2239. 2010. View Article : Google Scholar : PubMed/NCBI
11.	Minami S, Kijima T, Takahashi R, et al: Combination chemo-therapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study. BMC Cancer. 12:2962012. View Article : Google Scholar : PubMed/NCBI
12.	Eisenhauer EA, Therasse P, Bogaerts J, et al: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar
13.	Liang Z, Zhang J, Zeng X, et al: Relationship between EGFR expression, copy number and mutation in lung adenocarcinomas. BMC Cancer. 10:3762010. View Article : Google Scholar : PubMed/NCBI
14.	Li C, Sun Y, Fang Z, et al: Comprehensive analysis of epidermal growth factor receptor gene status in lung adenocarcinoma. J Thorac Oncol. 6:1016–1021. 2011. View Article : Google Scholar : PubMed/NCBI
15.	Orlando M, Lee JS, Yang C, Simms L and Park K: Efficacy of pemetrexed-cisplatin (PC) in East Asian patients (pts): Subgroup analysis of a phase III study comparing PC versus gemcitabine-cisplatin (GC) in first-line treatment of advanced nonsmall cell lung cancer (NSCLC). J Clin Oncol. 27:80452009.
16.	Wu YL, Zhou C, Cheng Y, et al: Erlotinib as second-line treatment in patients with advanced non-small-cell lung cancer and asymptomatic brain metastases: a phase II study (CTONG-0803). Ann Oncol. 24:993–999. 2013. View Article : Google Scholar : PubMed/NCBI
17.	Giovannetti E, Lemos C, Tekle C, et al: Molecular mechanisms underlying the synergistic interaction of erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, with the multi-targeted antifolate pemetrexed in non-small-cell lung cancer cells. Mol Pharmacol. 73:1290–1300. 2008. View Article : Google Scholar
18.	Li T, Ling YH, Goldman ID and Perez-Soler R: Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in human non-small cell lung cancer cells. Clin Cancer Res. 13:3413–3422. 2007. View Article : Google Scholar : PubMed/NCBI
19.	Van Schaeybroeck S, Karaiskou-McCaul A, Kelly D, Longley D, Galligan L, VanCutsem E and Johnston P: Epidermal growth factor receptor activity determines response of colorectal cancer cells to gefitinib alone and in combination with chemotherapy. Clin Cancer Res. 11:7480–7489. 2005.
20.	Magne N, Fischel JL, Dubreuil A, et al: ZD1839 (Iressa) modifies the activity of key enzymes linked to fluoropyrimidine activity: rational basis for a new combination therapy with capecitabine. Clin Cancer Res. 9:4735–4742. 2003.PubMed/NCBI
21.	Budman DR, Soong R, Calabro A, Tai J and Diasio R: Identification of potentially useful combinations of epidermal growth factor receptor tyrosine kinase antagonists with conventional cytotoxic agents using median effect analysis. Anticancer Drugs. 17:921–928. 2006. View Article : Google Scholar
22.	Yatabe Y, Matsuo K and Mitsudomi T: Heterogeneous distribution of EGFR mutations is extremely rare in lung adenocarcinoma. J Clin Oncol. 29:2972–2977. 2011. View Article : Google Scholar : PubMed/NCBI
23.	Henson JW, Ulmer S and Harris GJ: Brain tumor imaging in clinical trials. AJNR Am J Neuroradiol. 29:419–424. 2008. View Article : Google Scholar