Untitled

Mizumatsu, Shinichiro; Matsumoto, Kengo; Ono, Yasuhiro; Tamiya, Takashi; Furuta, Tomohisa; Ohmoto, Takashi

doi:10.1023/a:1006436911670

Cited by 2 publications

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various in vivo studies have been conducted using intrathecal delivered agents for leptomeningeal dissemination. A study using intrathecal MX2, an anthracycline inhibiting topoisomerase II, in a rat model of dissemination showed only a modest increase in survival, which could be explained by inadequate infiltration into parenchyma 153 . A patient study investigating intrathecal triothriethylenephosphoramide (thio-TEPA) for ependymal or leptomeningeal dissemination from anaplastic astrocytoma or GBM was conducted and found a modest improvement in survival at 10 months 154 .…”

Section: Approaches That Bypass Bbb/btbmentioning

confidence: 99%

Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy

Upton¹,

Ung²,

George³

et al. 2022

Theranostics

View full text Add to dashboard Cite

Despite significant advances in research, the prognosis for both primary and secondary brain cancers remains poor. The blood-brain barrier (BBB) is a complex and unique semi-permeable membrane that serves as a protective structure to maintain homeostasis within the brain. However, it presents a significant challenge for the delivery of therapeutics into the brain and tumor. Some brain tumors are known to compromise BBB integrity, producing a highly heterogeneous vasculature known as the blood-tumor-barrier (BTB). Identifying strategies to bypass these obstacles to improve the penetrability of anticancer therapeutics has been the focus of research in this area. In this review, we discuss the strategies that have been investigated to evade or alter the cellular and molecular barriers of both the BBB and the BTB and detail the methods currently under preclinical or clinical investigation, including molecular, biological, and physical processes to overcome the BBB or BTB. Increased understanding of the BBB and BTB and the current methods of overcoming these barriers will enable the development of new and more effective treatment strategies for brain tumors.

show abstract

Section: Approaches That Bypass Bbb/btbmentioning

confidence: 99%

Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy

Upton¹,

Ung²,

George³

et al. 2022

Theranostics

View full text Add to dashboard Cite

show abstract

Pharmacokinetics Following Intraventricular Administration of Chemotherapy in Patients with Neoplastic Meningitis

Fleischhack

Jaehde

Bode

2005

Clinical Pharmacokinetics

View full text Add to dashboard Cite

Intraventricular administration of chemotherapy is one approach to overcoming the limited distribution of anticancer drugs and their active metabolites into the CNS. This form of regional chemotherapy has led to effective treatment of occult and overt meningeal leukaemia in humans. In contrast, the efficacy of this therapy is extremely limited in the treatment of leptomeningeal dissemination of various solid tumours. Pharmacokinetic studies of the commonly intraventricularly applied anticancer agents in humans have demonstrated that, using low drug doses, very high drug concentrations can be achieved in the cerebrospinal fluid (CSF) and relatively high concentrations in the leptomeninges but not in the brain tissue and the plasma. Therefore, this approach is not an effective treatment for bulky disease of brain tissue, and results in minimal systemic toxicity. In comparison with intralumbar administration, lower interpatient variability of CSF drug concentrations and improved clinical efficacy were observed. 'Concentration x time' schedules, i.e. frequent small drug doses over a short period, enable long-term CSF exposure to cytotoxic drug concentrations while avoiding excessively high and potentially neurotoxic drug concentrations. The technique of ventriculolumbar cerebrospinal perfusion delivers continuously high drug concentrations throughout the CSF for several hours, but its widespread use is limited by the technical complexities of this approach. In this article, the dosages, schedules and pharmacokinetic data of routinely used intraventricular agents in humans, e.g. methotrexate, cytarabine, glucocorticoids and thiotepa, are outlined in detail. In addition, pharmacokinetic data of investigational agents for intraventricular administration (diaziquone, DTC 101, mercaptopurine, mafosfamide, etoposide, topotecan, nimustine [ACNU] and bleomycin) are presented. Better understanding of the CSF pharmacology of these drugs is an essential prerequisite for safe, effective administration of these drugs. Investigational efforts are underway to verify the feasibility and efficacy of different dosages, schedules and combination therapies of these new intra-CSF agents. Current and future clinical research should also focus on methods allowing the delivery of tumoricidal drug concentrations for extended periods into the CSF and the brain tissue while minimising neurotoxicity and systemic toxicity (e.g. liposomal drug preparations, monoclonal antibodies, immunotoxins and gene therapy).

show abstract

Untitled

Cited by 2 publications

References 16 publications

Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy

Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy

Pharmacokinetics Following Intraventricular Administration of Chemotherapy in Patients with Neoplastic Meningitis

Contact Info

Product

Resources

About