Intrathecal administration of etoposide in the treatment of malignant meningitis: feasibility and pharmacokinetic data

A, van der Gaast; Sonneveld, Pieter; Dr, Mans; Ta, Splinter

doi:10.1007/bf00685957

Cited by 29 publications

(4 citation statements)

References 7 publications

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“…In accordance with previous studies, the intraventricular administration of etoposide at a dose of 0.5 mg on 5 consecutive days at a 2-to 5-week interval is well tolerated and has low toxicity ( Van der Gaast et al, 1992;Slavc et al, 2000). The catheter-associated complication rate was similar to that reported by Chamberlain et al (1997) in a larger cohort of 120 patients using Ommaya reservoirs and other intraventricular catheter systems for intraventricular chemotherapy.…”

Section: Discussionsupporting

confidence: 80%

Feasibility of intraventricular administration of etoposide in patients with metastatic brain tumours

et al. 2001

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SummaryAs the systemic administration of etoposide is effective in the treatment of relapsed and metastatic brain tumours, a pilot trial was designed to study the feasibility of intraventricular administration of etoposide in such patients. 14 patients aged 2.1 to 33.2 years were treated with intraventricular etoposide simultaneously with either oral or intravenous chemotherapy with trofosfamide or carboplatin and etoposide. In 59 courses (1-12/patient) 0.5 mg etoposide was administered daily via an indwelling subcutaneous reservoir for 5 consecutive days every 2-5 weeks over a period of 0-11 months. During 15 courses in 5 patients serial CSF samples were obtained and etoposide levels were determined by reversed-phase HPLC. Side effects included transient headache and bacterial meningitis, each during 2 courses. Pharmacokinetic data analysis in the CSF (11 courses, 4 patients) revealed a terminal half-life of 7.4±1.2 hours and an AUC of 25.0 ± 9.5 µg h ml -1 (mean ± standard deviation). The volume of distribution at steady state and total clearance exhibited a large interindividual variability with mean values of 0.16 l and 0.46 ml min -1 respectively. Intraventricularly administered etoposide is well tolerated. CSF peak levels exceed more than 100-fold those achieved with intravenous infusions. Further studies should be focused on optimizing the dose and schedule and on determining the effectiveness of intraventricularly administered etoposide.

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Section: Discussionsupporting

confidence: 80%

Feasibility of intraventricular administration of etoposide in patients with metastatic brain tumours

et al. 2001

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“…There are currently limited data on CNS administration of etoposide. In 1992, van der Gaast and colleagues reported on the successful intrathecal administration of etoposide in 2 patients with malignant meningitis resulting from small cell lung cancer and chronic myelocytic leukemia, respectively [76]. Both patients received etoposide 0.5 mg diluted in 2 mL saline intraventricularly once daily for 5 days followed 3 weeks later by a second course where the same dose was given twice daily for another 5 days.…”

Section: Etoposidementioning

confidence: 98%

“…For both of these agents, dose and duration of treatment were variable. The remaining chemotherapy agents have been used for refractory or metastatic brain tumors or with meningeal metastases [75][76][77][78][79][80][81][82][83][84]. Again, outcomes and dosing were variable.…”

Section: Other Intra-csf Chemotherapy Agentsmentioning

confidence: 99%

Intra-CSF administration of chemotherapy medications

Gabay

Thakkar

Stachnik

et al. 2012

Cancer Chemother Pharmacol

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Leptomeningeal carcinomatosis is a devastating complication of cancer and is likely increasing in incidence. The combination of widespread neuro-axial spread based on CSF flow and the blood-brain barrier (BBB) has favored immediate local delivery of antineoplastic agents. With the BBB, the leptomeninges can be a sanctuary site to systemic cancers and goal of therapy includes preventing involvement in this space. Current therapies with U.S. Food and Drug Administration (FDA) approval are limited to treat hematologic cancers. Although lacking FDA guidance, a wider array of therapies is available to treat solid tumors. We provide an updated examination on both well-established intra-CSF chemotherapies as well as agents having limited data, but reports of therapeutic benefit.

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“…The first reported successful and safe administration of etoposide intraventricularly was by van der Gaast et al in 1992 [11]. Etoposide is a derivative of podophyllotoxin that functions as a toposisomerase II inhibitor, and induces breaks in single and double strands of DNA, all of which prevents new DNA synthesis as well as causing cell death in tumour cells [12].…”

Section: Introductionmentioning

confidence: 99%

Evaluating the efficacy and safety of single-agent etoposide intra-CSF chemotherapy in children and young people with relapsed/refractory central nervous system tumours

et al. 2023

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Purpose The aim of the project was to evaluate intra-CSF etoposide administration in a palliative setting for children and young people with relapsed/refractory central nervous system (CNS) tumours, with the primary endpoints being overall survival and progression-free survival time. A safety endpoint was to assess the side effect profile and complications of intra-CSF etoposide. Methods Thirty-five patients under the age of 30 years (median age: 5.33 years) were enrolled onto the project. The cross-centre study was a service evaluation, with a data collection spreadsheet designed in Nottingham and completed by both Nottingham and Oxford centres. Data was analysed using SPSS, assessing the overall survival and progression-free survival times, as well as the 6-month and 1-year survival rates. Results The median overall survival and progression-free survival times were 10.97 and 5.91 months, respectively. The 6-month and 1-year overall survival rates were 67% and 48%, and the progression-free survival rates were 50% and 22%. Age at the start of intra-CSF therapy was significantly associated with overall survival (P = 0.046), with the 6 + age group having improved overall survival. Treatment type was significantly associated with overall survival (P = 0.012), with etoposide intra-CSF treatment being associated with improved overall survival. Treatment duration was significantly associated with both overall survival (P < 0.001) and progression-free survival (P < 0.001). Conclusion Intra-CSF etoposide treatment has shown to increase both overall and progression-free survival significantly, whilst having few side effects and maintaining a good quality of life for patients, reflecting it as a beneficial therapy in the palliative setting.

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Intrathecal administration of etoposide in the treatment of malignant meningitis: feasibility and pharmacokinetic data

Cited by 29 publications

References 7 publications

Feasibility of intraventricular administration of etoposide in patients with metastatic brain tumours

Feasibility of intraventricular administration of etoposide in patients with metastatic brain tumours

Intra-CSF administration of chemotherapy medications

Evaluating the efficacy and safety of single-agent etoposide intra-CSF chemotherapy in children and young people with relapsed/refractory central nervous system tumours

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