Cerebrospinal Fluid Concentrations of Gefitinib in Patients With Lung Adenocarcinoma

Zhao, Jing; Chen, Minjiang; Zhong, Wei; Zhang, Li; Li, Longyun; Xiao, Yi; Nie, Lei; Hu, Pei; Wang, Mengzhao

doi:10.1016/j.cllc.2012.06.004

Cited by 108 publications

(84 citation statements)

References 38 publications

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“…This finding suggests that the standard dose of erlotinib for patients with brain metastases from non-small-cell lung cancer exerted a curative effect. However, similar to the type of micromolecular EGFR-TKI, the gefitinib concentration in the cerebrospinal fluid was distinctly less than its IC 50 value and the erlotinib concentration (16)(17)(18). This is mainly due to the fact that the plasma peak concentration of gefitinib with the standard dose was ~14% (1/7) that of erlotinib (19,20) and the blood-brain barrier permeability of gefitinib was ~1%, which was significantly lower compared to that of erlotinib (16).…”

Section: Discussionmentioning

confidence: 80%

The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer

Deng

Feng

et al. 2013

Molecular and Clinical Oncology

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Abstract. It has been demonstrated that erlotinib is effective in treating patients with brain metastasis from non-small-cell lung cancer. However, the number of studies determining the erlotinib concentration in these patients is limited. The purpose of this study was to measure the concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung carcinoma. Six patients were treated with the standard recommended daily dose of erlotinib (150 mg) for 4 weeks. All the patients had previously received chemotherapy, but no brain radiotherapy. At the end of the treatment period, blood plasma and cerebrospinal fluid samples were collected and the erlotinib concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS̸MS). The average erlotinib concentration in the blood plasma and the cerebrospinal fluid was 717.7±459.7 and 23.7±13.4 ng/ml, respectively. The blood-brain barrier permeation rate of erlotinib was found to be 4.4±3.2%. In patients with partial response (PR), stable disease (SD) and progressive disease (PD), the average concentrations of erlotinib in the cerebrospinal fluid were 35.5±19.0, 19.1±8.7 and 16.4±5.9 ng/ml, respectively. In addition, the efficacy rate of erlotinib for metastatic brain lesions was 33.3%, increasing to 50% in patients with EGFR mutations. However, erlotinib appeared to be ineffective in cases with wild-type EGFR. In conclusion, a relatively high concentration of erlotinib was detected in the cerebrospinal fluid of patients with brain metastases from non-small-cell lung cancer. Thus, erlotinib may be considered as a treatment option for this patient population.

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Section: Discussionmentioning

confidence: 80%

The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer

Deng

Feng

et al. 2013

Molecular and Clinical Oncology

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“…Several reports demonstrated that gefitinib or icotinib are associated with a favorable response in lung adenocarcinoma with BM, particularly in cases harboring EGFR mutations, such as our patient (15)(16)(17)(18)(19). EGFR-TKIs are reported to cross the blood-brain barrier, although it has been suggested that TKI concentration is reduced in the central nervous system compared with the serum levels (20). In such cases, increased doses may improve the efficacy (21).…”

Section: Discussionmentioning

confidence: 64%

Quick regression of brain metastases from lung adenocarcinoma with epidermal growth factor receptor-tyrosine kinase inhibitor treatment: A case report and literature review

Huang

Zhu

Wang

et al. 2016

Molecular and Clinical Oncology

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Abstract. Brain metastasis (BM) commonly occurs in patients with advanced lung cancer, and is associated with poor prognosis and limited treatment options, particularly for end-stage patients who are in poor physical and mental state. We herein present a case of lung adenocarcinoma with BM, as revealed by tumor marker and imaging studies. The patient was a 74-year-old woman who was diagnosed with lung adenocarcinoma with several metastatic lesions in the mediastinal lymph nodes, bone and brain. The patient underwent two cycles of chemotherapy, but the cancer recurred with enlarged BM, resulting in confusion and body dysfunction. The patient then received epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy with icotinib. After approximately 12 h of treatment the symptoms disappeared, and the metastatic lesions in the brain largely regressed in the following months. Our case indicates that the EGFR-TKI icotinib may provide a rapid and safe approach for emergency situations with BM from lung adenocarcinoma.

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“…Stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT) concomitantly or followed by EGFR-TKIs remain the current gold standard for patients with BM, even if they are often associated with considerable adverse neurotoxicity and questionable efficacy. Activity of upfront first-generation EGFR-TKIs has been reported in retrospective series including low number of EastAsian patients (Park et al, 2012;Iuchi et al, 2013;Gerber et al, 2014;Zhang et al, 2016a), overall showing poor response rates likely due to the low penetration of such agents across the bloodbrain barrier (BBB) (Zhao et al, 2013;de Vries et al, 2012). Some studies showed that erlotinib has a better central nervous system (CNS) penetration than gefitinib (Togashi et al, 2012), thus suggesting that it could be preferred if TKI monotherapy is used upfront for asymptomatic patients with BM.…”

Section: Activity Against Brain Metastasismentioning

confidence: 99%

EGFR inhibition in NSCLC: New findings…. and opened questions?

Passiglia

Listì

Castiglia

et al. 2017

Critical Reviews in Oncology/Hematology

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The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients’ outcomes. In this review we summarize the most important recent findings regarding EGFR-inhibition in NSCLC, highlighting the current unsolved questions on the selection of the best TKI in first-line, which therapy can be combined with upfront EGFR-TKIs, how to overcome acquired resistance, and which are the clinical applications of liquid biopsy

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Cerebrospinal Fluid Concentrations of Gefitinib in Patients With Lung Adenocarcinoma

Cited by 108 publications

References 38 publications

The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer

The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer

Quick regression of brain metastases from lung adenocarcinoma with epidermal growth factor receptor-tyrosine kinase inhibitor treatment: A case report and literature review

EGFR inhibition in NSCLC: New findings…. and opened questions?

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