scholarly journals A Clinical Research of Ceritinib Treating Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer With Brain Metastasis

2021 ◽  
Author(s):  
Saiqiong Cui ◽  
Xin Liu ◽  
Dan Li ◽  
Dafu Yang ◽  
Zhaoxia Dai
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
Alk Inhibitor ◽  
Line Therapy ◽  
Intracranial Lesions ◽  
Fat Meal

Abstract Objective As a second-generation oral anaplastic lymphoma kinase (ALK) inhibitor, ceritinib was recommended as posterior line therapy in patients with crizotinib resistance or intolerance. While in the real world, the clinical efficacy and safety of ceritinib, 450mg/d, taken with a low-fat meal in crizotinib resistant patients, especially with brain metastases, are still to be further investigated. Methods This retrospective analysis was conducted on patients with ALK- positive advanced non-small cell lung cancer (NSCLC) between May 2017 and December 2020 in our hospital, who were crizotinib resistant or intolerant. The aim was to analyze the clinical efficacy and safety of ceritinib as posterior line therapy in patients, especially in those with brain metastases, and to further explore the efficacy against rare fusion of ALK and the option after ALK inhibitor resistance. RECIST (1.1) criteria were adopted, and for relevant statistical analysis, RStudio was used. Results Of the 13 cases treated with ceritinib, 8 were treated as second-line therapy, 5 as third-line or fourth-line treatment. Of the total, 12 had brain metastases, 3 had received brain radiotherapy previously, and 1 had received surgical treatment for brain metastases previously. There were 8 cases evaluated as partial remission (PR), 2 evaluated as stable disease (SD), and 3 unevaluable for the response. There were 1 case of PKNOX2-ALK fusion and 1 case of IGR-ALK fusion observed as rare ALK fusion, and intracranial lesions were evaluated as PR for both. There were 6 cases received subsequent targeted therapy after progression of ceritinib, including 5 with alectinib and 1 with ensartinib, all of which showed response. In 13 cases, by the terminal time of follow-up, median progression-free survival (PFS) was 7.4 m, disease control rate (DCR) was 76.92%, overall response rate (ORR) was 61.54%, and median overall survival (OS) was 25.4m. In 12 cases with brain metastasis, 9 were suitable for intracranial response evaluation, of which, 1 case achieved CR for intracranial lesions, 7 achieved PR and 1 SD was observed, ORR was 88.89%, and DCR was 100%. The adverse events rate of any grade was 91.67%, the common adverse events were diarrhea (46.15%), AST level increased (41.67%), ALT level increased (33.33%), increased GGT (33.33%), increased ALP (25.00%), nausea (16.67%), increased creatinine (16.67%). Other reported AEs were cough, vomiting, dizziness, arthralgia and fatigue, 1 case (8.33%) each. Conclusion Ceritinib 450mg taken with taken with low-fat meal showed good efficacy and safety in crizotinib resistant patients with central nervous system metastasis, and also, it is effective in some cases with rare fusion of ALK.

scholarly journals The structure of blood–tumor barrier and distribution of chemotherapeutic drugs in non-small cell lung cancer brain metastases

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ling-yun Ye ◽  
Li-xiang Sun ◽  
Xiu-hua Zhong ◽  
Xue-song Chen ◽  
Song Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Blood Vessels ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Chemotherapeutic Drugs ◽  
Small Cell Lung ◽  
Metastatic Lesions

Abstract Background Brain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood–brain barrier (BBB) is frequently impaired, forming blood–tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors. Methods Bioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results Brain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases. Conclusions Brain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.

scholarly journals Icotinib is as efficacious as gefitinib for brain metastasis of EGFR mutated non-small-cell lung cancer

2020 ◽  
Author(s):  
Kejun Liu ◽  
Guanming Jiang ◽  
Ailing Zhang ◽  
Zhuanghua Li ◽  
Jun Jia
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Egfr Mutated ◽  
Egfr Tkis

Abstract Background: The prognosis of non-small-cell lung cancer (NSCLC) with brain metastases is very poor. Currently, therapeutic methods for this patient population include whole-brain radiation therapy (WBRT), surgery, radiosurgery and systemic treatment. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could be effective on cerebral metastases of mutated NSCLC. However, which EGFR-TKIs is more appropriate is still unknown. Methods: We conducted a retrospective analysis of advanced NSCLC patients with brain metastases for EGFR targeted therapy from November 2013 to April 2018 at Dongguan People’s Hospital, Southern Medical University, China. A total of 43 patients were recruit in this study. Among them, 21 cases received icotinib (125 mg, thrice a day) and 22 cases received gefitinib (250 mg, once a day) until disease progression or unacceptable toxicity. The primary end point of this study was intracranial PFS (iPFS). The relationships between therapeutic arms and patients characteristics were performed using Pearson’s chi-square test or Fisher’s exact test. The differences in PFS among the two arms were analyzed using Kaplan-Meier curves and log rank tests. Results: There was no significant difference of intracranial ORR (66.6% versus 59.1%, P =0.62) and DCR (85.7% versus 81.8%, P =0.73) between the two arms. The median intracranial PFS (iPFS) for icotinib and gefitinib arms were 8.4 months (95% CI, 5.4 to 11.3 months) and 10.6 months (95% CI, 6.3 to 14.8 months), respectively (P =0.17). Adverse events of the two study arms were generally mild. None of the patients experienced dose reduction of EGFR-TKIs. Conclusions: Our study showed that icotinib and gefitinib had similar efficacy for brain metastasis of EGFR mutated NSCLC. Large randomized studies are suggested to further illuminate the effect of these two EGFR-TKIs on cerebral lesions of NSCLC.

Multidisciplinary management of brain metastases from non-small cell lung cancer: A retrospective study of 251 patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19030-e19030
Author(s):  
M. Shenglin ◽  
X. Yaping ◽  
Y. Xinmin ◽  
Y. Yang
Keyword(s):  
Lung Cancer ◽  
Weight Loss ◽  
Prognostic Factors ◽  
Retrospective Study ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Blood Serum ◽  
Small Cell ◽  
Multidisciplinary Management ◽  
Small Cell Lung

e19030 Background: The detection of brain metastasis(BM) is becoming increasingly common in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate clinical course, prognostic significance, and treatment efficacy in patients with brain metastasis. Methods: The records of all patients with BM from December 2003 to January 2007 were reviewed, and a retrospective study of 251 patients with cytologically and histologically diagnosed NSCLC and brain metastasis detected by cranial computed tomography or magnetic resonance imaging was performed. Variables analyzed included the recursive partitioning analysis (RPA) grouping, weight loss, LDH in blood serum, sex, age, time of brain metastasis (synchronous vs. metachronous), number of brain metastases, maximum diameter of largest brain lesion, Karnofsky performance status, histologic type (adenocarcinoma vs. other types of NSCLC), TNM stage (without consideration of brain involvement), and the treatment modality used for both the primary NSCLC tumor and brain metastasis. Results: The overall 1-, 2- and 3-year survival rates were 34.1%, 13.7% and 8.7% with a median survival time of 9.0 months (95% CI 8.04–9.97 months). On multivariate analysis, RPA grouping, weight loss, LDH in blood serum and treatment were independent prognostic factors. The median overall survival (OS) time of chemotherapy alone, whole brain radiotherapy (WBRT) alone, surgery alone, WBRT with chemotherapy, surgery with chemoradiation, WBRT with Gefitinib and others management was 6.0, 9.0, 12.0, 9.0, 22.0, 13.0 and 4.0 months, respectively, which were significantly different (X2=43.104, P=0.000). The stratify analysis indicated the median OS of patients received concurrent WBRT/chemotherapy (13.0 months) was longer than it of patients received sequential WBRT/chemotherapy (9.0 months) (X2=3.89,P=0.049). Conclusions: The main prognostic factors of BM from NSCLC of pretreatment are RAP grouping, weight loss and LDH in blood serum. The effect of combined treatment of surgery with chemoradiation is favorable and the choice of the patient is important. The survival are prolonged by active multidisciplinary management of brain metastases. [Table: see text]

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