Su1646 – The Influence of Brain Metastases on the Central Nervous System Effects of Methylnaltrexone: A Post Hoc Analysis of 3 Randomized, Double-Blind Studies

2019 ◽  
Vol 156 (6) ◽  
pp. S-596
Author(s):  
Darren M. Brenner ◽  
Neal E. Slatkin ◽  
Nancy Stambler ◽  
Robert J. Israel
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
The Central Nervous System ◽  
Post Hoc

scholarly journals The influence of brain metastases on the central nervous system effects of methylnaltrexone: a post hoc analysis of 3 randomized, double-blind studies

2021 ◽  
Author(s):  
Darren M. Brenner ◽  
Neal E. Slatkin ◽  
Nancy Stambler ◽  
Robert J. Israel ◽  
Paul H. Coluzzi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Opioid Withdrawal ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Pain Scores ◽  
Opioid Receptor Antagonists ◽  
Post Hoc

Abstract Purpose Peripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor®) are indicated for the treatment of opioid-induced constipation (OIC). The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC. Methods This post hoc analysis of pooled data from 3 randomized, placebo-controlled trials included cancer patients with OIC who received MNTX or placebo. Endpoints included changes from baseline in pain scores, rescue-free laxation (RFL) within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms. Results Among 356 cancer patients in the pooled population, 47 (MNTX n = 27; placebo n = 20) had brain metastases and 309 (MNTX n = 172; placebo n = 137) did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose (70.4% vs 15.0%, respectively, p = 0.0002). TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal. Conclusion Focal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX.

scholarly journals Current management of brain metastases

2014 ◽  
Vol 33 (04) ◽  
pp. 347-351
Author(s):  
Pedro Tadao Hamamoto Filho ◽  
Vitor César Machado ◽  
Flávio Ramalho Romero ◽  
Luis Gustavo Ducati ◽  
Marco Antônio Zanini ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Treatment Modalities ◽  
Current Management ◽  
Brain Radiotherapy ◽  
Recent Advances ◽  
The Central Nervous System ◽  
Treatment Surgery

AbstractBrain metastases are the most common tumors within the central nervous system. Recent advances on diagnosis and treatment modalities have allowed for longer survival. In this paper we review the indication of each modality of treatment: surgery, whole brain radiotherapy and stereotactic radiosurgery, as also recent advances on the knowledge of brain metastases biology that may improve the use of medical treatment and chemotherapy.

scholarly journals The Biology of Brain Metastasis

2013 ◽  
Vol 59 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Robert R Langley ◽  
Isaiah J Fidler
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Disease Progression ◽  
Microvascular Endothelial Cells ◽  
Number Of Patients ◽  
The Central Nervous System ◽  
Microvascular Endothelial

BACKGROUND It is estimated that at least 200 000 cases of brain metastases occur each year in the US, which is 10 times the number of patients diagnosed with primary brain tumors. Brain metastasis is associated with poor prognosis, neurological deterioration, diminished quality of life, and extremely short survival. Favorable interactions between tumor cells and cerebral microvascular endothelial cells encourage tumor growth in the central nervous system, while tumor cell interactions with astrocytes protect brain metastases from the cytotoxic effects of chemotherapy. CONTENT We review the pathogenesis of brain metastasis and emphasize the contributions of microvascular endothelial cells and astrocytes to disease progression and therapeutic resistance. Animal models used to study brain metastasis are also discussed. SUMMARY Brain metastasis has many unmet clinical needs. There are few clinically relevant tumor models and no targeted therapies specific for brain metastases, and the mean survival for untreated patients is 5 weeks. Improved clinical outcomes are dependent on an enhanced understanding of the metastasis-initiating population of cells and the identification of microenvironmental factors that encourage disease progression in the central nervous system.

A double-blind, comparative study of gadodiamide injection and gadopentetate dimeglumine in MRI of the central nervous system

1993 ◽  
Vol 35 (3) ◽  
pp. 173-177 ◽  
Author(s):  
J. Valk ◽  
P. R. Algra ◽  
C. J. Hazenberg ◽  
W. B. M. Slooff ◽  
M. G. Svaland
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Comparative Study ◽  
Gadopentetate Dimeglumine ◽  
Double Blind ◽  
The Central Nervous System

scholarly journals The microenvironment of brain metastases from solid tumors

2021 ◽  
Vol 3 (Supplement_5) ◽  
pp. v121-v132
Author(s):  
Ethan S Srinivasan ◽  
Krutika Deshpande ◽  
Josh Neman ◽  
Frank Winkler ◽  
Mustafa Khasraw
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Intracranial Tumor ◽  
Malignant Cells ◽  
Complex Interplay ◽  
Dismal Prognosis ◽  
Medical Need ◽  
Metabolic Conditions ◽  
The Central Nervous System

Abstract Brain metastasis (BrM) is an area of unmet medical need that poses unique therapeutic challenges and heralds a dismal prognosis. The intracranial tumor microenvironment (TME) presents several challenges, including the therapy-resistant blood–brain barrier, a unique immune milieu, distinct intercellular interactions, and specific metabolic conditions, that are responsible for treatment failures and poor clinical outcomes. There is a complex interplay between malignant cells that metastasize to the central nervous system (CNS) and the native TME. Cancer cells take advantage of vascular, neuronal, immune, and anatomical vulnerabilities to proliferate with mechanisms specific to the CNS. In this review, we discuss unique aspects of the TME in the context of brain metastases and pathways through which the TME may hold the key to the discovery of new and effective therapies for patients with BrM.

Modern Management of Central Nervous System Metastases in the Era of Targeted Therapy and Immune Oncology

2019 ◽  
pp. e59-e69 ◽  
Author(s):  
Priscilla Brastianos ◽  
Michael A. Davies ◽  
Kim Margolin ◽  
Helena A. Yu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
New Era ◽  
Patients With Cancer ◽  
Whole Brain Radiation ◽  
The Central Nervous System ◽  
Considerable Morbidity ◽  
Immune Oncology

Metastases to the central nervous system (CNS) are associated with considerable morbidity and mortality in patients with cancer. Historically, very few systemic therapies have shown efficacy in this patient population. Emerging data are now demonstrating that whole-brain radiation therapy, previously considered the mainstay of treatment of brain metastases, is associated with high rates of neurotoxicity. In this new era of targeted therapy and immunotherapy, clinical outcomes are improving, and patients are living longer. Despite these improvements, there is an urgent need to design central nervous system–penetrant compounds that target the genetic mutations enriched in brain metastases and to bring these to clinical trials.

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