Chemotherapy Delivery Issues in Central Nervous System Malignancy: A Reality Check

2007 ◽  
Vol 25 (16) ◽  
pp. 2295-2305 ◽  
Author(s):  
Leslie L. Muldoon ◽  
Carole Soussain ◽  
Kristoph Jahnke ◽  
Conrad Johanson ◽  
Tali Siegal ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Tumor Therapy ◽  
Reality Check ◽  
Current State ◽  
Biologic Effect ◽  
Prospective Trials ◽  
Cns Lymphomas ◽  
Alternative Delivery

PurposeThis review assesses the current state of knowledge regarding preclinical and clinical pharmacology for brain tumor chemotherapy and evaluates relevant brain tumor pharmacology studies before October 2006.ResultsChemotherapeutic regimens in brain tumor therapy have often emerged from empirical clinical studies with retrospective pharmacologic explanations, rather than prospective trials of rational chemotherapeutic approaches. Brain tumors are largely composed of CNS metastases of systemic cancers. Primary brain tumors, such as glioblastoma multiforme or primary CNS lymphomas, are less common. Few of these tumors have well-defined optimal treatment. Brain tumors are protected from systemic chemotherapy by the blood-brain barrier (BBB) and by intrinsic properties of the tumors. Pharmacologic studies of delivery of conventional chemotherapeutics and novel therapeutics showing actual tumor concentrations and biologic effect are lacking.ConclusionIn this article, we review drug delivery across the BBB, as well as blood-tumor and –cerebrospinal fluid (CSF) barriers, and mechanisms to increase drug delivery to CNS and CSF tumors. Because of the difficulty in treating CNS tumors, innovative treatments and alternative delivery techniques involving brain/cord capillaries, choroid plexus, and CSF are needed.

scholarly journals Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1885
Author(s):  
Julian S. Rechberger ◽  
Frederic Thiele ◽  
David J. Daniels
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Brain Tumors ◽  
Phase 1 ◽  
Citation Count ◽  
Tumor Therapy ◽  
The United States ◽  
Blood Brain Barrier Disruption ◽  
Current State ◽  
Brain Barrier Disruption

Intra-arterial drug delivery circumvents the first-pass effect and is believed to increase both efficacy and tolerability of primary and metastatic brain tumor therapy. The aim of this update is to report on pertinent articles and clinical trials to better understand the research landscape to date and future directions. Elsevier’s Scopus and ClinicalTrials.gov databases were reviewed in August 2021 for all possible articles and clinical trials of intra-arterial drug injection as a treatment strategy for brain tumors. Entries were screened against predefined selection criteria and various parameters were summarized. Twenty clinical trials and 271 articles satisfied all inclusion criteria. In terms of articles, 201 (74%) were primarily clinical and 70 (26%) were basic science, published in a total of 120 different journals. Median values were: publication year, 1986 (range, 1962–2021); citation count, 15 (range, 0–607); number of authors, 5 (range, 1–18). Pertaining to clinical trials, 9 (45%) were phase 1 trials, with median expected start and completion years in 2011 (range, 1998–2019) and 2022 (range, 2008–2025), respectively. Only one (5%) trial has reported results to date. Glioma was the most common tumor indication reported in both articles (68%) and trials (75%). There were 215 (79%) articles investigating chemotherapy, while 13 (65%) trials evaluated targeted therapy. Transient blood–brain barrier disruption was the commonest strategy for articles (27%) and trials (60%) to optimize intra-arterial therapy. Articles and trials predominately originated in the United States (50% and 90%, respectively). In this bibliometric and clinical trials analysis, we discuss the current state and trends of intra-arterial therapy for brain tumors. Most articles were clinical, and traditional anti-cancer agents and drug delivery strategies were commonly studied. This was reflected in clinical trials, of which only a single study had reported outcomes. We anticipate future efforts to involve novel therapeutic and procedural strategies based on recent advances in the field.

scholarly journals A review of potential applications of MR-guided focused ultrasound for targeting brain tumor therapy

2018 ◽  
Vol 44 (2) ◽  
pp. E10 ◽  
Author(s):  
Layton Lamsam ◽  
Eli Johnson ◽  
Ian D. Connolly ◽  
Max Wintermark ◽  
Melanie Hayden Gephart
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Focused Ultrasound ◽  
Tumor Therapy ◽  
Survival Times ◽  
Potential Applications ◽  
Animal Tumor ◽  
Antitumor Chemotherapy ◽  
Systemic Drug Delivery

Magnetic resonance–guided focused ultrasound (MRgFUS) has been used extensively to ablate brain tissue in movement disorders, such as essential tremor. At a lower energy, MRgFUS can disrupt the blood-brain barrier (BBB) to allow passage of drugs. This focal disruption of the BBB can target systemic medications to specific portions of the brain, such as for brain tumors. Current methods to bypass the BBB are invasive, as the BBB is relatively impermeable to systemically delivered antineoplastic agents. Multiple healthy and brain tumor animal models have suggested that MRgFUS disrupts the BBB and focally increases the concentration of systemically delivered antitumor chemotherapy, immunotherapy, and gene therapy. In animal tumor models, combining MRgFUS with systemic drug delivery increases median survival times and delays tumor progression. Liposomes, modified microbubbles, and magnetic nanoparticles, combined with MRgFUS, more effectively deliver chemotherapy to brain tumors. MRgFUS has great potential to enhance brain tumor drug delivery, while limiting treatment toxicity to the healthy brain.

Recent Advances in Brain Tumor Therapy: Local Intracerebral Drug Delivery by Polymers

2004 ◽  
Vol 22 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Christopher Guerin ◽  
Alessandro Olivi ◽  
Jon D. Weingart ◽  
H. Christopher Lawson ◽  
Henry Brem
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Tumor Therapy ◽  
Recent Advances ◽  
Brain Tumor Therapy

The New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium: Organization, Objectives, and Activities

1998 ◽  
Vol 5 (2) ◽  
pp. 107-114 ◽  
Author(s):  
Stuart A. Grossman ◽  
Joy D. Fisher ◽  
Steven Piantadosi ◽  
Henry Brem
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Clinical Research ◽  
Tumor Therapy ◽  
Laboratory Research ◽  
Primary Brain Tumors ◽  
Large Numbers ◽  
Neuro Imaging ◽  
Important Drug

Background: Despite advances in neuro-imaging, neurosurgery, radiation therapy, and chemotherapy, limited progress has been made in the treatment of patients with high-grade astrocytomas. The National Cancer Institute has attempted to speed advances in this field by funding CNS consortia to conduct innovative clinical trials in this patient population since 1994. Methods: The NABTT CNS Consortium is composed of a consortium headquarters and nine member institutions with outstanding multidisciplinary expertise, clinical and laboratory research capabilities, and access to large numbers of patients with brain tumors. Results: The objectives of the NABTT Consortium are to improve the therapeutic outcome for adults with primary brain tumors, to conduct basic science and clinical research, and to improve the care and quality of life of adults with primary brain tumors. NABTT's clinical studies have discovered important drug interactions between anticonvulsant and antineoplastic agents, defined the activity of paclitaxel and 9-aminocamptothecin in glioblastoma multiforme, tested a novel dose escalation strategy for brain tumor trials, and established new protocol “classes” to expedite and standardize clinical research in this field. Conclusions: Significant progress in the care of patients with primary brain tumors is likely to result from the highly focused and multidisciplinary efforts of the NIH-funded CNS consortia.

scholarly journals Brain tumors risk factors - current state of knowledge review

2021 ◽  
Vol 11 (9) ◽  
pp. 101-107
Author(s):  
Zygmunt Siedlecki ◽  
Małgorzata Szafrańska ◽  
Emilia Główczewska-Siedlecka ◽  
Maciej Śniegocki
Keyword(s):  
Risk Factors ◽  
Brain Tumor ◽  
Ionizing Radiation ◽  
Brain Tumors ◽  
Poor Prognosis ◽  
Primary Brain Tumor ◽  
Evidence Based ◽  
Raw Meat ◽  
The Public ◽  
Current State

Brain tumors cause widespread apprehension in society, associated with poor prognosis and death. Laymen most often associate them with glioblastoma multiforme which is in fact the most common malignant primary brain tumor (formerly it was considered the most common primary brain tumor, now it is thought that meningiomas are the most common). The interest of both the public and physicians is aroused by potential brain tumors risk factors. The only evidence based risk factor is ionizing radiation of head and neck. Other risk factors are also under consideration, however are not conclusive and different studies give different results. Given the widespread apprehension of brain tumors, knowledge of the risk factors seems obvious. In this manuscript, we have reviewed the current state of knowledge aboutf risk factors based on research. They confirm that apart from ionizing radiation, the existence of other risk factors is considered: cell phones, electromagnetic field, occupational exposure to raw meat, viruses. However, all these risk factors are not confirmed by reference results.

Enhanced therapeutic agent delivery through magnetic resonance imaging–monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status

2012 ◽  
Vol 32 (1) ◽  
pp. E4 ◽  
Author(s):  
Hao-Li Liu ◽  
Hung-Wei Yang ◽  
Mu-Yi Hua ◽  
Kuo-Chen Wei
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Therapeutic Agent ◽  
Brain Barrier ◽  
Term Survival ◽  
Blood Brain ◽  
The Brain

Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

scholarly journals Emerging Nano-Carrier Strategies for Brain Tumor Drug Delivery and Considerations for Clinical Translation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1193
Author(s):  
David J. Lundy ◽  
Helen Nguyễn ◽  
Patrick C. H. Hsieh
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Clinical Use ◽  
Brain Disorders ◽  
Regulatory Issues ◽  
Chemotherapy Drugs ◽  
Brain Drug Delivery ◽  
Clinical Models ◽  
Tumor Drug Delivery

Treatment of brain tumors is challenging since the blood–brain tumor barrier prevents chemotherapy drugs from reaching the tumor site in sufficient concentrations. Nanomedicines have great potential for therapy of brain disorders but are still uncommon in clinical use despite decades of research and development. Here, we provide an update on nano-carrier strategies for improving brain drug delivery for treatment of brain tumors, focusing on liposomes, extracellular vesicles and biomimetic strategies as the most clinically feasible strategies. Finally, we describe the obstacles in translation of these technologies including pre-clinical models, analytical methods and regulatory issues.

Novel Advances in Drug Delivery to Brain Cancer

2005 ◽  
Vol 4 (4) ◽  
pp. 417-428 ◽  
Author(s):  
Maciej S. Lesniak
Keyword(s):  
Drug Delivery ◽  
Brain Tumors ◽  
Tumor Therapy ◽  
Chemotherapeutic Agents ◽  
Controlled Delivery ◽  
Local Drug Delivery ◽  
Delivery Methods ◽  
Malignant Brain Tumors ◽  
Direct Exposure ◽  
The Brain

The therapy of brain tumors has been limited by a lack of effective methods of drug delivery to the brain. Systemic administration is often associated with toxic side effects and ultimately fails to achieve therapeutic concentrations within a tumor. An attractive strategy that has gained importance in brain tumor therapy has relied on local and controlled delivery of chemotherapeutic agents by biodegradable polymers. This technique allows direct exposure of tumor cells to a therapeutic agent for a prolonged period of time and has been shown to prolong the survival of patients with malignant brain tumors. The use of polymers for local drug delivery greatly expands the spectrum of drugs available for the treatment of malignant brain tumors. This review discusses the rationale for local drug delivery, describes the development of currently available polymer-based therapeutic agents, and highlights examples of promising non-polymer based drug delivery methods for use in the treatment of malignant brain tumors.

scholarly journals Breaching the Blood–Brain Tumor Barrier for Tumor Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2391
Author(s):  
Fabrizio Marcucci ◽  
Angelo Corti ◽  
Andrés J. M. Ferreri
Keyword(s):  
Drug Delivery ◽  
Brain Tumors ◽  
Tumor Therapy ◽  
Clinical Testing ◽  
Medical Need ◽  
Tumor Tissues ◽  
Anti Cancer ◽  
The Central Nervous System ◽  
Radio Sensitivity

Tumors affecting the central nervous system (CNS), either primary or secondary, are highly prevalent and represent an unmet medical need. Prognosis of these tumors remains poor, mostly due to the low intrinsic chemo/radio-sensitivity of tumor cells, a meagerly known role of the microenvironment and the poor CNS bioavailability of most used anti-cancer agents. The BBTB is the main obstacle for anticancer drugs to achieve therapeutic concentrations in the tumor tissues. During the last decades, many efforts have been devoted to the identification of modalities allowing to increase drug delivery into brain tumors. Until recently, success has been modest, as few of these approaches reached clinical testing and even less gained regulatory approval. In recent years, the scenario has changed, as various conjugates and drug delivery technologies have advanced into clinical testing, with encouraging results and without being burdened by a heavy adverse event profile. In this article, we review the different approaches aimed at increasing drug delivery to brain tumors, with particular attention to new, promising approaches that increase the permeability of the BBTB or exploit physiological transport mechanisms.

scholarly journals Adult final height after GH therapy for irradiation-induced GH deficiency in childhood survivors of brain tumors: the Belgian experience

2010 ◽  
Vol 162 (3) ◽  
pp. 483-490 ◽  
Author(s):  
D Beckers ◽  
M Thomas ◽  
J Jamart ◽  
I Francois ◽  
M Maes ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Gh Deficiency ◽  
Final Height ◽  
Tumor Therapy ◽  
First Year ◽  
Gh Therapy ◽  
Height Gain ◽  
Design And Methods ◽  
Childhood Survivors

ObjectivesThe treatment of brain tumors in childhood is frequently complicated by growth retardation with a high proportion of irradiation (Irr)-induced GH deficiency (GHD) resulting in reduced adult final height (AFH) even after GH therapy (GHT). In order to optimize future GHT protocols, more information on the factors influencing the growth response to GH in these children is needed.This retrospective study evaluated AFH and influencing auxological and treatment factors of a standardized daily biosynthetic GHT in childhood survivors of brain tumors with documented GHD after brain Irr.Design and methodsFrom the Belgian GH Registry, 57 children survivors of a brain tumor outside the hypothalamo-pituitary area with available AFH were stratified into two groups depending on cranial (C-Irr; n=25) or craniospinal (CS-Irr; n=32) Irr.ResultsIn the C-Irr patients, results showed an AFH of −0.8 (−2.5, 1.4) SDS (median (range)) and in the CS-Irr patients, results showed a significantly (P<0.001) lower AFH of −1.8 (−4.2, 0.0) SDS. AFH SDS corrected for mid-parental height (MPH) in the C-Irr group was −0.5 (−2.2, 0.9) and −1.5 (−3.6, 0.0) SDS in the CS-Irr group. AFH was positively correlated with age at end of tumor therapy, height SDS at start GHT, height gain SDS first year GHT, and negatively correlated with CS-Irr.ConclusionsGHT failed to restore adult height to MPH in nearly half of Irr-induced GHD patients for brain tumor, especially those receiving CS-Irr, irradiated at a younger age or shorter at start GHT.

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