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Cerebrospinal fluid concentrations of gefitinib in patients with lung adenocarcinoma
Jing Zhao1, Minjiang Chen, Wei Zhong
1Division of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Background:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have high response and disease control rates in patients with central nervous system (CNS) metastases. However there have been only a few case reports on the penetration of gefitinib into the cerebrospinal fluid (CSF). The aim of this study was to investigate the CSF concentration of gefitinib in Chinese patients with lung adenocarcinomas.
Methods:
From March 2007 to December 2010, 22 patients were sequentially enrolled in this study at Peking Union Medical College Hospital (PUMCH). CSF and plasma samples were collected at the same time from each patient after at least 7 doses of gefitinib. The concentrations of gefitinib in the CSF and plasma were measured by high performance liquid chromatography coupled with tandem mass spectrometry. The clinical factors that may affect gefitinib penetration were analyzed.
Results:
The mean plasma and CSF concentrations of gefitinib were 491.8 ± 184.2 ng/mL and 6.2 ± 4.6 ng/mL, respectively, and the mean ratio of CSF-plasma concentration was 1.3% ± 0.7%. There was a good correlation between CSF and plasma gefitinib concentrations (R = 0.556, P = .006). The presence of CNS metastases was associated with increased gefitinib CSF penetration (1.46% vs. 0.95%; P = .042).
Conclusions:
The concentration of gefitinib in CSF was low, and it was significantly related to the plasma gefitinib concentration. Because of the inadequate CNS drug exposure, patients in whom the extracranial lesions were well controlled may benefit from increasing gefitinib dose for the new intracranial lesions.
Insights
Gefitinib concentration in cerebrospinal fluid (CSF) is low in lung adenocarcinoma patients. Higher doses may be needed for effective treatment of brain metastases, as CSF drug exposure is inadequate.
Area of Science:
- Oncology
- Pharmacology
- Neuroscience
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) show efficacy in central nervous system (CNS) metastases.
- Limited data exists on gefitinib penetration into cerebrospinal fluid (CSF).
Purpose of the Study:
- To investigate the CSF concentration of gefitinib in Chinese patients with lung adenocarcinomas.
- To analyze clinical factors influencing gefitinib penetration into the CNS.
Main Methods:
- Sequential enrollment of 22 lung adenocarcinoma patients treated with gefitinib.
- Simultaneous collection of CSF and plasma samples after at least 7 gefitinib doses.
- Quantification of gefitinib concentrations using high-performance liquid chromatography-tandem mass spectrometry.
Main Results:
- Mean CSF gefitinib concentration was 6.2 ± 4.6 ng/mL, with a CSF-plasma ratio of 1.3%.
- A significant correlation was observed between plasma and CSF gefitinib concentrations (R = 0.556, P = .006).
- Presence of CNS metastases was associated with increased gefitinib CSF penetration (1.46% vs. 0.95%, P = .042).
Conclusions:
- Gefitinib CSF concentration is low and directly related to plasma levels.
- Inadequate CNS drug exposure suggests potential benefit from increased gefitinib dosage for intracranial lesions.
- Further research may explore dose optimization for enhanced brain tumor treatment.
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