ArticleJournal of neuro-oncology2004
Toxicity and cerebrospinal fluid levels of carboplatin chronically infused into the brainstem of a primate.
Article in Journal of neuro-oncology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- Phase I trial of intracerebral convection-enhanced delivery of carboplatin for treatment of recurrent high-grade gliomas.PloS one · 2020Article
- Convection-enhanced drug delivery for gliomas.Surgical neurology international · 2015Article
- Intracerebral delivery of carboplatin in combination with either 6 MV photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma.Journal of experimental & clinical cancer research : CR · 2012Article
- The effects of temozolomide delivered by prolonged intracerebral microinfusion against the rat brainstem GBM allograft model.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2012Article
- An evaluation of the safety and feasibility of convection-enhanced delivery of carboplatin into the white matter as a potential treatment for high-grade glioma.Journal of neuro-oncology · 2012Article
- Neurological grading, survival, MR imaging, and histological evaluation in the rat brainstem glioma model.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2009Article
- Local chemotherapy in the rat brainstem with multiple catheters: a feasibility study.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2009Article
- Enhanced survival and cure of F98 glioma-bearing rats following intracerebral delivery of carboplatin in combination with photon irradiation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2007Article
- Brain Stem Tumors.Current treatment options in neurology · 2005Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCarboplatin was infused into the brainstem of cynomolgus monkeys to investigate neurotoxicity and systemic exposures following chronic local delivery.
methodsInfusions at 0.42 microl/h were intended to deliver 0.025 (n = 2), 0.075 (n = 3), 0.25 (n = 5), and 0.75 (n = 3) mg/kg by day 30. Laboratory tests, radiographic measurements, and clinical observations were used to monitor toxicity. Blood and cerebrospinal fluid (CSF) were sampled for platinum.
resultsLethargy and ataxia were observed after week 4 in the monkeys given 0.075 mg/kg, and week 2 in the monkeys given 0.25 mg/kg when the infused doses were approximately 250 and 400 microg, respectively. Rapidly progressive neurotoxicity with the 0.75 mg/kg dose required termination of the infusions at days 4-10. Hematology and chemistry values were unremarkable in all groups. Blood levels of platinum remained undetectable in 0.025 and 0.075 mg/kg dose groups. Levels in the 0.25 mg/kg group were 3.1 +/- 0.6 microg/l at 2 weeks and 5.2 +/- 0.8 microg/l at 1 month. The CSF platinum levels varied. Animals in the 0.25 mg/kg group had higher CSF levels at 2 weeks (avg. 65 microg/l, range 36-89) compared to their 1 month value (avg. 60 microg/l, range 7-170), despite the constant infusion.
conclusionCarboplatin can be chronically infused into monkey brainstems. Neurotoxicity is the predominant side effect and is dose-dependent. Pharmacokinetics of local and systemic delivery are different for carboplatin. Further studies are needed to monitor toxicity at higher flow rates and to investigate drug binding to abnormal central nervous system (CNS) tissues.
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