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01-06-2011 | Short Communication

Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy

Authors: Takeshi Masuda, Noboru Hattori, Akinobu Hamada, Hiroshi Iwamoto, Shinichiro Ohshimo, Masashi Kanehara, Nobuhisa Ishikawa, Kazunori Fujitaka, Yoshinori Haruta, Hiroshi Murai, Nobuoki Kohno

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2011

Abstract

Purpose

We have treated patients with non-small-cell lung cancer (NSCLC) who developed leptomeningeal metastases (LM) during gefitinib therapy, and then found symptomatic improvement following treatment change to erlotinib. Based on this experience, we wondered whether erlotinib could be detected in cerebrospinal fluid (CSF) when it was used for NSCLC patients with LM. This study was conducted to determine erlotinib concentrations in CSF and assess responses to erlotinib in patients with NSCLC developing LM during gefitinib therapy.

Methods

Three advanced NSCLC patients with LM that developed during gefitinib therapy were treated with erlotinib. On day 28 after the initiation of erlotinib treatment, plasma and CSF were obtained and the concentrations of erlotinib in these samples were measured. Eastern Cooperative Oncology Group (ECOG) performance status (PS) and neurologic symptoms were determined.

Results

Erlotinib CSF penetration was 6.3% ± 6.1% (mean ± SD). In cases 1 and 2, we observed improvements in ECOG PS and neurologic symptoms. In case 3, cytological improvement was seen in the CSF. In each patient, deletion of exon 19 or exon 21 L858R mutation of the epidermal growth factor receptor (EGFR) gene was detected in carcinoma cells from the CSF.

Conclusions

We report on 3 patients with NSCLC who had developed LM during gefitinib treatment and showed clinical improvements following change to erlotinib therapy. In all cases, small but measurable penetration of erlotinib into CSF was observed. Because EGFR mutations were detected in all cases, we suggest that erlotinib is a therapeutic option for LM carcinoma cells with EGFR mutations.

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Title: Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy
Authors: Takeshi Masuda
Noboru Hattori
Akinobu Hamada
Hiroshi Iwamoto
Shinichiro Ohshimo
Masashi Kanehara
Nobuhisa Ishikawa
Kazunori Fujitaka
Yoshinori Haruta
Hiroshi Murai
Nobuoki Kohno
Publication date: 01-06-2011
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-011-1555-6

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Abstract

Purpose

Methods

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Conclusions

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