Oral Targeted Therapies and Central Nervous System (CNS) Metastases

CNS Drugs ◽  
2015 ◽  
Vol 29 (11) ◽  
pp. 935-952 ◽  
Author(s):  
Michael P. Gabay ◽  
Scott M. Wirth ◽  
Joan M. Stachnik ◽  
Colleen L. Overley ◽  
Katie E. Long ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Targeted Therapies ◽  
Cns Metastases

scholarly journals Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Yang ◽  
Qilong Liu ◽  
Lei Cao ◽  
Wei Sun ◽  
Xiaowei Gu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cns Metastases ◽  
Tki Treatment ◽  
Egfr Tki

Abstract Background The purpose of this study was to compare the efficacy of osimertinib (OSI) versus afatinib (AFA) in patients with T790M-positive, non-small-cell lung cancer (NSCLC) and multiple central nervous system (CNS) metastases after failure of initial epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. Methods Consecutive patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment were retrospectively identified from our medical institution during 2016–2018 and underwent either oral 80 daily OSI or oral 40 daily AFA every 3 weeks for up to 6 cycles, until disease progression, intolerable adverse events (AEs), or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS). Results The cohort consisted of 124 patients (OSI: n = 60, mean age = 64.24 years [SD: 12.33]; AFA: n = 64, mean age = 64.13 years [SD: 13.72]). After a median follow-up of 24 months (range, 3 to 28), a significant improvement in OS was detected (hazard ratio [HR] 0.59, 95% confidence interval [CI], 0.39–0.91; p = 0.0160; median, 13.7 months [95% CI, 11.1–14.8] for OSI vs 9.6 months [95% CI, 8.4–10.2] for AFA). The median duration of PFS was significantly longer with OSI than with AFA (HR 0.62; 95% CI, 0.41–0.91; p = 0.014; median, 4.5 months [95% CI, 3.5–5.7] vs 3.9 months [95% CI, 3.1–4.8]). The proportion of grade 3 or higher adverse events (AEs) was lower with OSI (22.4%) than with AFA (39.4%). Conclusions In patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment, OSI may be associated with significantly improved survival benefit compared with AFA, with a controllable tolerability profile.

scholarly journals A case of metastatic adenocarcinoma of the prostate arising in a meningioma

2013 ◽  
Vol 3 (3) ◽  
pp. 4 ◽  
Author(s):  
Devin Pugsley ◽  
Greg Bailly ◽  
Rekha Gupta ◽  
Derek Wilke ◽  
Lori Wood
Keyword(s):  
Prostate Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Prostate Carcinoma ◽  
Metastatic Adenocarcinoma ◽  
Cns Metastases ◽  
Diagnostic Uncertainty ◽  
Sont Encore ◽  
Adenocarcinoma Of The Prostate ◽  
Cns Tumours

We present the case of a 70-year-old man who had a prostate adenocarcinomathat metastatized to a previously unknown cranialmeningioma. Central nervous system (CNS) metastases are veryuncommon in patients with prostate cancer, and metastases topre-existing primary CNS tumours are even more uncommon. Rareevents like this can cause diagnostic uncertainty, as shown by thiscase. This case is a reminder for clinicians to consider prostatemetastases in patients with known prostate carcinoma and focalneurological symptoms.Nous décrivons le cas d'un homme de 70 ans présentant un adénocarcinomemétastatique de la prostate secondaire à un méningiomeintra-crânien non diagnostiqué auparavant. Les métastasesau niveau du SNC sont très rares chez les patients atteints de cancerde la prostate et les métastases sont encore plus rares dansle cas de tumeurs primitives pré-existantes au niveau du SNC.La rareté de ces cas peut soulever des incertitudes au niveau dudiagnostic, comme nous le montrerons. Ce cas permet de rappeleraux cliniciens d'envisager la possibilité de métastases chezles patients atteints d'un carcinome prostatique confirmé et présentantdes signes neurologiques focaux.

scholarly journals Next-generation strategies for gene-targeted therapies of central nervous system disorders: A workshop summary

2021 ◽  
Author(s):  
Jill A. Morris ◽  
Chris H. Boshoff ◽  
Nina F. Schor ◽  
Ling M. Wong ◽  
Guangping Gao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Targeted Therapies ◽  
Next Generation ◽  
Central Nervous System Disorders ◽  
Workshop Summary

Efficacy of PD-1 or PD-L1 inhibitors and central nervous system metastases in advanced cancer: a meta-analysis

2021 ◽  
Vol 21 ◽  
Author(s):  
Minyong Peng ◽  
Shan Li ◽  
Hui Xiang ◽  
Wen Huang ◽  
Weiling Mao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Cell Death ◽  
Nervous System ◽  
Programmed Cell Death ◽  
Future Research ◽  
Significant Heterogeneity ◽  
Cns Metastases ◽  
Hazard Ratios ◽  
Significant Difference

<P>Background: Little is known about the efficacy of programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors in patients with central nervous system (CNS) metastases. <P> Objective: Assess the difference in efficacy of PD-1 or PD-L1 inhibitors in patients with and without CNS metastases. <P> Methods: From inception to March 2020, PubMed and Embase were searched for randomized controlled trials (RCTs) about PD-1 or PD-L1 inhibitors. Only trails with available hazard ratios (HRs) for overall survival (OS) of patients with and without CNS metastases simultaneously would be included. Overall survival hazard ratios and their 95% confidence interval (CI) were calculated, and the efficacy difference between these two groups was assessed in the meantime. <P> Results: 4988 patients (559 patients with CNS metastases and 4429 patients without CNS metastases) from 8 RCTs were included. In patients with CNS metastases, the pooled HR was 0.76 (95%CI, 0.62 to 0.93), while in patients without CNS metastases, the pooled HR was 0.74 (95%CI, 0.68 to 0.79). There was no significant difference in efficacy between these two groups (Χ=0.06 P=0.80). <P> Conclusion: With no significant heterogeneity observed between patients with or without CNS metastases, patients with CNS metastases should not be excluded from PD-1 or PD-L1 blockade therapy. Future research should permit more patients with CNS metastases to engage in PD-1 or PD-L1 blockade therapy and explore the safety of PD-1 or PD-L1 inhibitors in patients with CNS metastases.</P>

Penetration of VP 16-213 into cerebrospinal fluid after high-dose intravenous administration.

1984 ◽  
Vol 2 (3) ◽  
pp. 215-220 ◽  
Author(s):  
P E Postmus ◽  
J J Holthuis ◽  
H Haaxma-Reiche ◽  
N H Mulder ◽  
L M Vencken ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
Cns Metastases ◽  
Csf Levels ◽  
Dose Levels

VP 16-213 in standard doses is active against a number of solid tumors. Its penetration into the cerebrospinal fluid (CSF) is very limited at these dose levels. In 10 patients treated with high-dose VP 16-213 (0.9-2.5 g/m2), CSF levels of up to 0.54 microgram/mL were detected. In two patients with central nervous system (CNS) metastases of small cell lung cancer (SCLC) a response was seen after 1.0 and 1.5 g/m2 intravenously. High-dose VP 16-213 can possibly play a role in the treatment of CNS metastases of SCLC. Its application in late intensification regimens as a form of prophylaxis of CNS metastases should be investigated.

scholarly journals Effect of Central Nervous System Metastases on Treatment Discontinuation and Survival in Older Women Receiving Trastuzumab for Metastatic Breast Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Mark D. Danese ◽  
Karla Lindquist ◽  
Justin Doan ◽  
Deepa Lalla ◽  
Melissa Brammer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Metastatic Breast Cancer ◽  
Proportional Hazards ◽  
Metastatic Breast ◽  
Cns Metastases ◽  
Her2 Positive ◽  
Time To Death ◽  
Risk Of Death

Background. Trastuzumab improves survival in HER2-positive women with metastatic breast cancer (MBC). The consequences of longer survival include a higher likelihood of additional metastases, including those in the central nervous system (CNS). The effect of CNS metastases on both trastuzumab discontinuation and survival in older patients has not been described.Patients and Methods. We used the Surveillance Epidemiology and End Results (SEER) Medicare data to identify a cohort of 562 women age 66 or older with MBC who were diagnosed between January 1, 2000 and December 31, 2005, free of CNS metastases, and initiated trastuzumab after MBC diagnosis. Time to discontinuation and time to death were analyzed using proportional hazards models.Results. Newly diagnosed CNS metastases were associated with both higher risk of trastuzumab discontinuation (relative hazard[RH]=1.78, 95% CI 1.11–2.87) and higher risk of death (RH=2.49, 95% CI 1.84–3.37). The incidence rate of new CNS metastases was comparable among various sites of metastasis (10.7 to 14.7 per 1,000 patient-months), except for bone which was higher (24.1 per 1,000).Conclusion. The diagnosis of CNS metastases was associated with an increase in both the likelihood of discontinuing trastuzumab therapy as well as the risk of death.

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