Intra-arterial BCNU in the treatment of recurrent medulloblastoma

Watne, Kjell; Hager, Bjarne; Hirschberg, Henry

doi:10.1007/bf00177836

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…However, several clinical trials and cases did not report significant improvement in survival. Intra-arterial drug delivery in a small set of medulloblastoma patients treated with celyvir (autologous mesenchymal stem cells infected with adenovirus ICOVIR5), a 7-day treatment course of oral procarbazine, intravenous vincristine in combination with four cycles of intra-arterial carmustine, or conventional chemotherapeutics in combination with mannitol, did not lead to remission of the disease in most patients [ 117 – 119 ]. In ependymoma, a small cohort of patients were treated with intra-arterial drug delivery with carmustine, bevacizumab, and cetuximab, and responded to the treatment [ 120 , 121 ].…”

Section: Drug Delivery Methods To Overcome the Bbbmentioning

confidence: 99%

Overview of Current Drug Delivery Methods Across the Blood–Brain Barrier for the Treatment of Primary Brain Tumors

et al. 2020

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Existing drug delivery methods have not led to a significant increase in survival for patients with malignant primary brain tumors. While the combination of conventional therapies consisting of surgery, radiotherapy, and chemotherapy has improved survival for some types of brain tumors (e.g., WNT medulloblastoma), other types of brain tumors (e.g., glioblastoma and diffuse midline glioma) still have a poor prognosis. The reason for the differences in response can be largely attributed to the blood-brain barrier (BBB), a specialized structure at the microvasculature level that regulates the transport of molecules across the blood vessels into the brain parenchyma. This structure hampers the delivery of most chemotherapeutic agents for the treatment of primary brain tumors. Several drug delivery methods such as nanoparticles, convection enhanced delivery, focused ultrasound, intranasal delivery, and intra-arterial delivery have been developed to overcome the BBB in primary brain tumors. However, prognosis of most primary brain tumors still remains poor. The heterogeneity of the BBB in primary brain tumors and the distinct vasculature of tumors make it difficult to design a drug delivery method that targets the entire tumor. Drug delivery methods that combine strategies such as focused ultrasound and nanoparticles might be a more successful approach. However, more research is needed to optimize and develop new drug delivery techniques to improve survival of patients with primary brain tumors.

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Section: Drug Delivery Methods To Overcome the Bbbmentioning

confidence: 99%

Overview of Current Drug Delivery Methods Across the Blood–Brain Barrier for the Treatment of Primary Brain Tumors

et al. 2020

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Comparison of in vitro activity of epipodophyllotoxins with other chemotherapeutic agents in human medulloblastomas

Tomlinson

Lihou²,

Smith³

1991

Br J Cancer

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Summary Surgical specimens from 15 medulloblastoma patients were used to establish early passage cultures. In vitro sensitivity to a battery of cytotoxic agents, including some in current medulloblastoma treatment protocols, was measured. Drug sensitivity was assessed at clinically relevant drug concentrations using the 3H-thymidine uptake method. Tumours were predicted to be sensitive if >37% were killed by exposure to drugs at clinically achievable levels. A poor response to vincristine (Vcr), cis-platin (CDDP), hydroxyurea (HU) Medulloblastoma is an important paediatric brain tumour because of its high incidence and malignant behaviour. The overall disease free survival at 5 years, in patients receiving surgery and craniospinal axis radiotherapy, is approximately 50%. This is considered to be the upper limit of curability by these treatment modalities. Chemotherapy has been shown to be advantageous in selected patient groups either as adjuvant therapy or as treatment of recurrent disease. The value of chemotherapy in the treatment of medulloblastoma will be dependent on the availability and identification of drugs active against this tumour. At present, protocols for chemotherapy usually include the lipophilic compounds carmustine (BCNU) or lomustine and procarbazine. Vincristine (Vcr), whilst poorly absorbed by cerebrospinal fluid and brain, is also commonly used (Bloom, 1986;Workman, 1986). Currently '8 in 1F therapy is being evaluated (Pendergrass et al., 1987).Cytotoxicity has been assessed by clonal assays in agar or on plastic, incorporation of 3H-thymidine into DNA, uptake of vital dyes and other methods with much the same results. Predictions of resistance are close to 100% correct; prediction of sensitivity, whilst less reliable, still has a success rate of around 70% Moon et al., 1981; Rosenbloom et al., 1983;Bogdahn, 1983;Kornblith et al., 1981;Kimmel et al., 1987). We have examined drug sensitivity in human medulloblastoma by using 14 early passage cultures. Our study provides data on the degree of heterogeneity of response between medulloblastomas obtained from a number of patients. Furthermore, the cells were from early passage cultures, and hence should give a better indication of chemosensitivity of the tumours in vivo. The epipodophyllotoxins teniposide (VM-26) and etoposide (VP16-213) were identified as potentially useful agents in this disease. We investigated the basis of primary clinical resistance to these drugs by quantitating intracellular steady-state drug concentrations, drug-induced protein-linked DNA strand breaks, and topoisomerase II expression and activity. Materials and methods Establishment of cell culturesAll studies were made on material collected at procedures performed for clinical reasons and remaining after sufficient tissue has been taken for clinical laboratory study. The histological diagnosis was confirmed by an independent neuropathologist (Professor B.W. Scheithauer). Over a period of 2 years, 16 medulloblastoma specimens were received from a total of 15 patients...

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Intra-arterial BCNU in the treatment of recurrent medulloblastoma

Cited by 2 publications

References 18 publications

Overview of Current Drug Delivery Methods Across the Blood–Brain Barrier for the Treatment of Primary Brain Tumors

Overview of Current Drug Delivery Methods Across the Blood–Brain Barrier for the Treatment of Primary Brain Tumors

Comparison of in vitro activity of epipodophyllotoxins with other chemotherapeutic agents in human medulloblastomas

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