Treatment for Patients With Cerebral Metastases

Markesbery, William R.; Brooks, William H.; Gupta, Gaurav; Young, Andrew

doi:10.1001/archneur.1978.00500350058012

Cited by 203 publications

(74 citation statements)

References 12 publications

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“…Dissemination of cancer to the brain or leptomeningeal invasion of metastatic or primary central nervous system (CNS) neoplasms is usually a terminal event for cancer patients (1), resulting in a median survival of generally Ͻ1 year (2)(3)(4)(5)(6)(7)(8)(9). This dismal prognosis reflects the limitations placed on radiotherapy by (a) the significant risk of brain damage and spinal cord radionecrosis, (b) the inability to deliver therapeutic drug levels to the brain and cerebrospinal fluid with systemic administration, and (c) the minimal efficacy of currently available chemotherapeutic agents approved for intracerebral or intrathecal use (2)(3)(4)(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Treatment of Intracerebral Neoplasia and Neoplastic Meningitis with Regional Delivery of Oncolytic Recombinant Poliovirus

Ochiai¹,

Moore

Archer³

et al. 2004

Clinical Cancer Research

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Purpose: Spread to the central nervous system (CNS) and the leptomeninges is a frequent complication of systemic cancers that is associated with serious morbidity and high mortality. We have evaluated a novel therapeutic approach against CNS complications of breast cancer based on the human neuropathogen poliovirus (PV).Experimental Design: Susceptibility to PV infection and ensuing rapid cell lysis is mediated by the cellular receptor of PV, CD155. We evaluated CD155 expression in several human breast tumor tissue specimens and cultured breast cancer cell lines. In addition, we tested an oncolytic PV recombinant for efficacy in xenotransplantation models of neoplastic meningitis and cerebral metastasis secondary to breast cancer.Results: We observed that breast cancer tissues and cell lines derived thereof express CD155 at levels mediating exquisite sensitivity toward PV-induced oncolysis in the latter. An association with the immunoglobulin superfamily molecule CD155 renders breast cancer a likely target for oncolytic PV recombinants. This assumption was confirmed in xenotransplantation models for neoplastic meningitis or solitary cerebral metastasis, where local virus treatment dramatically improved survival.Conclusions: Our findings suggest oncolytic PV recombinants as a viable treatment option for CNS complications of breast cancer.

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Section: Introductionmentioning

confidence: 99%

Treatment of Intracerebral Neoplasia and Neoplastic Meningitis with Regional Delivery of Oncolytic Recombinant Poliovirus

Ochiai¹,

Moore

Archer³

et al. 2004

Clinical Cancer Research

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“…Several studies present in literature demonstrated that the median survival after brain metastases involvement diagnosis in patients treated with corticosteroids alone is about 2 months, and that this value is similar to the median survival obtained in patients treated with palliative therapy with any kind of central nervous system metastatic disease. (Cohen, 2004;Kaminsky-Forrett, 2000;Pectasides, 2005;Pectasides, 2006;Markesbery, 1978;Ruderman, 1965) …”

Section: Corticosteroids Mannitol and Antiepileptic Agentsmentioning

confidence: 99%

Central Nervous System Involvement from Epithelial Ovarian Cancer

Cormio¹,

Falagario²,

Selvaggi³

2012

Ovarian Cancer - Clinical and Therapeutic Perspectives

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“…Regional delivery of therapeutics has been investigated as an alternative for achieving high drug concentrations in the intrathecal space with the additional benefits of preventing drug metabolism by the liver or modification of the drug within the plasma, 1,2,26) but currently available chemotherapeutic agents approved for intrathecal use have minimal efficacy. 10,14,18,19,27,31) Furthermore, despite the potential of new therapies such as gene therapy, these approaches still remain very early in their development and tend not to be focused on treating neoplastic meningitis. Therefore, chemotherapy remains the primary modality for treating…”

Section: Introductionmentioning

confidence: 99%

Treatment of Neoplastic Meningitis With Intrathecal 9-Nitro-camptothecin

Ochiai

Pernell

Archer

et al. 2006

Neurol. Med. Chir.(Tokyo)

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The topoisomerase I inhibitor, 9-nitro-camptothecin (9NC), is highly tumoricidal against glioblastoma multiforme (GBM) in vitro. However, systemic administration of 9NC has not shown the expected efficacy in clinical trials. This failure may be due to the rapid hydrolysis of 9NC in plasma from the active form to the inactive and myelosuppressive form in the presence of human albumin at physiologic pH. Concurrent treatment with anticonvulsants and dexamethasone, drugs indispensable for the supportive therapy of patients with GBM, has also been shown to decrease plasma concentrations of these drugs. Intrathecal drug delivery circumvents the blood-brain barrier and minimizes systemic toxicity. Intrathecal delivery of 9NC may also have the more specific advantage of significantly reducing the hydrolysis of 9NC that occurs after systemic delivery due to the more favorable pH and reduced albumin content in cerebrospinal fluid. The present study evaluated the toxicity and efficacy of intrathecal delivery of 9NC in an athymic rat model of neoplastic meningitis. Toxicity tests showed that 0.3 mmol (5000 mM), 0.03 mmol (500 mM), 0.003 mmol (50 mM), or 0.0003 mmol (5 mM) of 9NC administered intrathecally to the athymic rats caused no evidence of clinical or histological toxicity. Intrathecal administration of 0.3 mmol (5000 mM) of 9NC twice a week for three doses to athymic rats with neoplastic meningitis induced by the GBM cell line, U87MGDEGFR, resulted in a 26% increase of median survival compared to the control group (p º 0.005). These results suggest that intrathecal treatment with 9NC may be useful for patients with GBM neoplastic meningitis.

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Treatment for Patients With Cerebral Metastases

Cited by 203 publications

References 12 publications

Treatment of Intracerebral Neoplasia and Neoplastic Meningitis with Regional Delivery of Oncolytic Recombinant Poliovirus

Treatment of Intracerebral Neoplasia and Neoplastic Meningitis with Regional Delivery of Oncolytic Recombinant Poliovirus

Central Nervous System Involvement from Epithelial Ovarian Cancer

Treatment of Neoplastic Meningitis With Intrathecal 9-Nitro-camptothecin

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