Elsevier

Lung Cancer

Volume 89, Issue 3, September 2015, Pages 268-273
Lung Cancer

Icotinib might be effective for the treatment of leptomeningeal carcinomatosis in non-small cell lung cancer with sensitive EGFR mutations

https://doi.org/10.1016/j.lungcan.2015.06.001Get rights and content

Abstract

Background

The incidence of leptomeningeal carcinomatosis (LMC) has increased in patients with metastatic non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of icotinib in the treatment of LMC.

Methods

Twenty-one NSCLC patients diagnosed with LMC and treated with icotinib were retrospectively reviewed.

Results

An exon 21 point mutation and an exon 19 deletion of EGFR were found in 10 and 11 patients, respectively. A standard dose of icotinib (125 mg/day, three times a day) was prescribed to 16 patients without previous icotinib therapy. A double dose of icotinib was prescribed to five patients who developed LMC during icotinib therapy with a standard dose. Eighteen of 20 patients showed improvement of dizziness and headache. Seventeen of 21 patients had an improved Eastern Cooperative Oncology Group performance status (ECOG PS) score after icotinib treatment. The median overall survival of the patients after the diagnosis of LMC was 10.1 months (95% confidence interval (CI): 8.4–12.0 months). Univariate analysis showed that the ECOG PS score, parenchymal brain metastasis, and previous icotinib administration were significantly associated with patient survival. Multivariate analysis also demonstrated that the ECOG PS score was an independent predictor for survival.

Conclusion

Our results suggest that icotinib is effective for the treatment of LMC from NSCLC with an EGFR mutation, especially for patients with a good ECOG PS score.

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.

Section snippets

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.

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  • Cited by (0)

    1

    These authors contributed equally to this work.

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