Icotinib might be effective for the treatment of leptomeningeal carcinomatosis in non-small cell lung cancer with sensitive EGFR mutations
Introduction
Lung cancer is one of the most common cancers that lead to central nervous system metastases, and approximately 5% of non-small cell lung carcinoma (NSCLC) patients develop leptomeningeal carcinomatosis (LMC).1, 2, 3 Several therapies, including whole-brain radiotherapy (WBRT) and intrathecal (IT) chemotherapy, have been used to treat LMC; however, the efficacies are marginal with an unsatisfactory outcome. For example, WBRT has not been shown to increase the survival of NSCLC patients with LMC.4 Although methotrexate and cytosine arabinoside are currently the major components of IT chemotherapy to treat LMC, these agents are not effective for NSCLC.5, 6 Systemic chemotherapeutic drugs have limitations with respect to controlling malignant cells inside the leptomeninges because they cannot easily penetrate the blood–brain barrier.7, 8 Because no effective treatments for LMC exist, the development of novel and efficient therapeutic strategies for LMC is urgently needed.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become the first choice of therapy for NSCLC patients with an EGFR mutation.9 Moreover, several retrospective studies have reported the effectiveness of the EGFR TKIs erlotinib and gefitinib in the treatment of LMC from NSCLC in patients with an EGFR mutation.10, 11, 12 Icotinib hydrochloride (Conmana®) is an oral EGFR TKI that was developed by Betta Pharmaceuticals. Icotinib has a similar structure as erlotinib and has comparable cerebrospinal fluid (CSF) penetration rates as erlotinib and gefitinib.13 A large, randomized, and head-to-head phase III clinical trial (ICOGEN) demonstrated that icotinib has a comparable efficacy to gefitinib in Chinese NSCLC patients. However, the efficacy of icotinib in the treatment of LMC from NSCLC is totally unknown.
The aim of this study was to evaluate the role of icotinib in the treatment of LMC by retrospectively reviewing 21 NSCLC patients with cytologically proven LMC who were treated with icotinib between 2011 and 2014 in our hospital.
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Patients
We reviewed the medical records of 21 patients who were diagnosed with LMC from NSCLC and were treated with icotinib between 2011 and 2014 at Zhejiang Cancer Hospital, China. Patients were included in this study only if they had a sensitive EGFR mutation (exon 19 deletion or exon 21L858R mutation). The diagnosis of LMC was based on the presence of malignant cells in the CSF. Patients who developed LMC during icotinib therapy were permitted to be included. Patients with radiological evidence of
Baseline characteristics
The clinical characteristics of the 21 patients are summarized in Table 1. 16 patients had not been treated with icotinib before LMC occurrence, and 5 patients developed LMC during icotinib therapy with standard dose. The median age of patients at diagnosis was 50 years old (range, 34–62 years old). Nineteen patients had adenocarcinoma, and two patients had unspecified NSCLC. An exon 21 point mutation and an exon 19 deletion mutation existed in 10 and 11 patients, respectively.
Treatment of LMC
For the treatment
Discussion
LMC from NSCLC is a difficult disease to treat and remains a grave entity in the clinical course of NSCLC. The survival time of NSCLC patients affected by LMC is approximately 3 months, which is shorter than that of patients with LMC from other diseases, such as breast cancer and hematological malignancies.14, 15, 16 More than half of patients with LMC from NSCLC die of leptomeningeal progression. In this study, at a median follow-up of 18.5 months, the median overall survival of the patients
Conflict of interest statement
None declared.
References (24)
- et al.
Prolonged survival of patients with non-small-cell lung cancer with leptomeningeal carcinomatosis in the modern treatment era
Clin Lung Cancer
(2014) - et al.
Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial
Lancet Oncol
(2012) - et al.
Erlotinib versus gefitinib for control of leptomeningeal carcinomatosis in non-small-cell lung cancer
J Thorac Oncol
(2013) - et al.
Leptomeningeal carcinomatosis: prognostic value of clinical, cerebrospinal fluid, and neuroimaging features
Clin Neurol Neurosurg
(2013) - et al.
Clinical outcomes of leptomeningeal metastasis in patients with non-small cell lung cancer in the modern chemotherapy era
Lung Cancer
(2012) - et al.
Erlotinib treatment of meningeal carcinomatosis in lung cancer: more is better
Ann Oncol
(2014) - et al.
Leptomeningeal carcinomatosis in non-small-cell lung cancer patients: impact on survival and correlated prognostic factors
J Thorac Oncol
(2013) - et al.
Cytologically proven meningeal carcinomatosis in patients with lung cancer: clinical observation of 34 cases
J Formos Med Assoc
(2008) - et al.
Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy
J Thorac Oncol
(2012) - et al.
Impact of EGFR tyrosine kinase inhibitors versus chemotherapy on the development of leptomeningeal metastasis in never smokers with advanced adenocarcinoma of the lung
J Neurooncol
(2013)
Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall-cell lung cancer: clinical implications for the subsequent management of the brain
Cancer
Prognostic significance of coexistent bulky metastatic central nervous system disease in patients with leptomeningeal metastases
Arch Neurol
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These authors contributed equally to this work.