scholarly journals A Case of Orbital Metastasis as Disease Progression of Anaplastic Lymphoma Kinase-Positive Lung Cancer Treated with Crizotinib

2015 ◽  
Vol 8 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Yoshihiko Sakata ◽  
Kodai Kawamura ◽  
Kazuya Ichikado ◽  
Masakazu Yoshioka
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Disease Progression ◽  
Anaplastic Lymphoma Kinase ◽  
Kinase Inhibitor ◽  
Case Reports ◽  
Orbital Metastasis ◽  
Visual Disorder ◽  
Anaplastic Lymphoma ◽  
Alk Positive

Orbital metastasis of lung cancer is rare. It often causes visual disorder. To date, there are only a few case reports. Crizotinib is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that leads to responses in most patients with ALK-positive non-small-cell lung cancer. Visual disorder is one of the popular adverse events of crizotinib, but the symptom almost decreases over time. We report a case of orbital metastasis as the disease progression of ALK-positive lung cancer treated with crizotinib. It should be kept in mind that orbital metastasis can be the disease progression of lung adenocarcinoma with ALK translocation treated with crizotinib. When physicians encounter a patient receiving crizotinib with visual disorder, we must distinguish between adverse events and orbital metastasis.

scholarly journals Humanistic burden of living with anaplastic lymphoma kinase-positive non-small-cell lung cancer: findings from the ALKConnect patient insight network and research platform

2021 ◽  
Vol 10 (1) ◽  
pp. LMT42
Author(s):  
Huamao M Lin ◽  
Xiaoyun Pan ◽  
Alyssa Biller ◽  
Kyla J Covey ◽  
Hui Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Patient Preferences ◽  
Anaplastic Lymphoma Kinase ◽  
Kinase Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

Aim: Evaluate real-world patient preferences, experiences and outcomes (health-related quality of life [HRQoL]) from patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) utilizing the ALKConnect Patient Insight Network. Patients & methods: Demographics, disease history/status/treatment, patient preferences and HRQoL (MD Anderson Symptom Inventory lung cancer module, reported as symptom severity and interference) were evaluated for US adults with ALK+ NSCLC. Results: Among 104 patients (median age: 53.0 years, 67.3% female, 40.0% employed), HRQoL and 3-month delay in disease progression were important treatment attributes. Burdensome symptoms included fatigue and disturbed sleep. Symptoms interfered most with work and day-to-day activity. Higher HRQoL was associated with ALK tyrosine kinase inhibitor (TKI) treatment and employment. Conclusion: ALKConnect demonstrated that disease progression, HRQoL, fatigue/sleep, ALK TKIs and employment matter in ALK+ NSCLC.

scholarly journals Systematic Review and Network Meta-Analysis of Anaplastic Lymphoma Kinase (ALK) Inhibitors for Treatment-Naïve ALK-Positive Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1966
Author(s):  
Cheng-Hao Chuang ◽  
Hsiao-Ling Chen ◽  
Hsiu-Mei Chang ◽  
Yu-Chen Tsai ◽  
Kuan-Li Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Anaplastic Lymphoma Kinase ◽  
Low Dose ◽  
Meta Analysis ◽  
Phase Iii ◽  
Pairwise Comparisons ◽  
Anaplastic Lymphoma ◽  
Treatment Naïve ◽  
Alk Positive

Several anaplastic lymphoma kinase inhibitors (ALKIs) have demonstrated excellent efficacy on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and also better adverse effect (AE) profiles compared to cytotoxic chemotherapy in advanced stage anaplastic lymphoma kinase (ALK) rearrangement-positive non-small cell lung cancer (NSCLC) in phase III randomized clinical trials (RCTs). We conducted this systematic review and network meta-analysis to provide a ranking of ALKIs for treatment-naïve ALK-positive patients in terms of PFS, ORR, and AEs. In addition, a sub-group analysis of treatment benefits in patients with baseline brain metastasis was also conducted. Contrast-based analysis was performed for multiple treatment comparisons with the restricted maximum likelihood approach. Treatment rank was estimated using the surface under the cumulative ranking curve (SUCRA), as well as the probability of being the best (Prbest) reference. All next-generation ALKIs were superior to crizotinib in PFS but lorlatinib and brigatinib had increased AEs. The probability of lorlatinib being ranked first among all treatment arms was highest (SUCRA = 93.3%, Prbest = 71.8%), although there were no significant differences in pairwise comparisons with high- (600 mg twice daily) and low- (300 mg twice daily) dose alectinib. In subgroup analysis of patients with baseline brain metastasis, low-dose alectinib had the best PFS (SUCRA = 87.3%, Prbest = 74.9%). Lorlatinib was associated with the best ranking for ORR (SUCRA = 90.3%, Prbest = 71.3%), although there were no significant differences in pairwise comparisons with the other ALKIs. In addition, low-dose alectinib had the best safety performance (SUCRA = 99.4%, Prbest = 97.9%). Lorlatinib and low-dose alectinib had the best PFS and ORR in the overall population and baseline brain metastasis subgroup, respectively. Low-dose alectinib had the lowest AE risk among the available ALKIs. Further head-to-head large-scale phase III RCTs are needed to verify our conclusions.

Does Crizotinib Auto-Inhibit CYP3A in vivo?

Pharmacology ◽  
2020 ◽  
Vol 105 (11-12) ◽  
pp. 715-718
Author(s):  
Abigail R. Bland ◽  
Nensi Shrestha ◽  
Rhonda J. Rosengren ◽  
John C. Ashton
Keyword(s):  
Lung Cancer ◽  
Cytochrome P450 ◽  
Western Blot ◽  
Anaplastic Lymphoma Kinase ◽  
Kinase Inhibitor ◽  
Cyp3a Activity ◽  
Cytochrome P450 3A ◽  
Anaplastic Lymphoma

Crizotinib is a tyrosine kinase inhibitor used to treat anaplastic lymphoma kinase-positive lung cancer. There is in vitro evidence that crizotinib may auto-inhibit cytochrome P450 3A (CYP3A) activity, with important implications for crizotinib pharmacokinetics. In order to test whether crizotinib treatment alters CYP3A activity in vivo, mice were treated with 5 and 25 mg/kg crizotinib (p.o.) daily for 14 days. Results showed that crizotinib treatment did not alter CYP3A activity as determined by erythromycin <i>N</i>-demethylation. In addition, CYP3A polypeptide expression as measured by Western blot was unchanged. Therefore, our results do not support CYP3A inhibition by crizotinib in vivo.

Sign in / Sign up

Export Citation Format

Share Document