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Non-small cell lung cancer leptomeningeal metastases treated with intrathecal therapy plus osimertinib and temozolomide and whole-brain radiation therapy: a case report

Authors Wang Y, Liu S, Wei X, Yan B, Li J, Su Z, Liu A, Zhang Y

Received 8 February 2018

Accepted for publication 23 May 2018

Published 10 August 2018 Volume 2018:11 Pages 4733—4738


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Arseniy Yuzhalin

Yunmei Wang,1,* Shuguang Liu,2,* Xiaohui Wei,1 Bin Yan,3 Jun Li,3 Zhixiang Su,1 Aiqin Liu,1 Yanjun Zhang1

1Department of Medical Oncology, Shaanxi Provincial Cancer Hospital Affiliated to Medical School, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People’s Republic of China; 2Department of orthopedics,Hong Hui Hospital, the Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710004, People’s Republic of China; 3Department of Radiology, Shaanxi Provincial Cancer Hospital Affiliated to Medical School, Xi’an Jiao tong University, Xi’an, Shaanxi 710061, People’s Republic of China

*These authors contributed equally to this work

Rationale: Leptomeningeal metastasis (LM) is an important cause of mortality in patients with non-small cell lung cancer (NSCLC). As the symptoms of LM and its early clinical manifestations are nonspecific, early diagnosis of LM is difficult. However, there are few treatment options for LM, which leads to a poor prognosis; thus, increased clinical attention is necessary. The effects of most systemic chemotherapies on metastatic brain tumors (brain metastases and LMs) are limited as they cannot pass the blood–brain barrier; therefore, whole-brain radiation therapy is a therapeutic option. Osimertinib is a potent and irreversible third-generation oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It binds to EGFR with high affinity when the EGFR T790M mutation is present together with sensitizing mutations. The clinical efficacy of osimertinib in NSCLC patients carrying the T790M mutation has been demonstrated in clinical trial NCT02468661. Intrathecal injection of chemotherapeutic drugs can be directed to a specific lesion. Temozolomide is one such drug, and its effect has been confirmed.
Patient and interventions: We treated a 38-year-old patient with NSCLC who carried the EGFR L858R mutation. We administered a combination of oral osimertinib and oral temozolomide plus an intrathecal injection of cytarabine and whole-brain radiation therapy for symptomatic multiple brain metastases.
Outcomes: The patient showed a marked response to this combination therapy. To date (after ~18 months), no recurrence or new lesions have been observed and he is asymptomatic. His disease-free survival surpasses that achieved with any monotherapy for LM.
Lessons: This is the first report to demonstrate the response to combination therapy in an NSCLC patient with LM. These findings indicate the potential utility of chemotherapy combined with radiotherapy combined with targeted therapy combined with local treatment, as each treatment acts via a different mechanism, enhancing their therapeutic effects.

Keywords: intrathecal injection, meningeal metastasis osimertinib, non-small cell lung cancer, temozolomide, WBRT

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