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8 Convection enhanced delivery of carboplatin for the treatment of diffuse intrinsic pontine glioma: the pharmacist’s perspective
  1. Rebekah Rogers
  1. Paediatric Neuroscience Pharmacist, University Hospitals Bristol NHS Foundation Trust

Abstract

Situation To ensure safe delivery of carboplatin by convection enhanced delivery (CED) for the treatment of diffuse intrinsic pontine glioma (DIPG).

Background CED describes a method of direct drug delivery to the brain parenchyma through surgically placed microcatheters, completely bypassing the blood brain barrier (BBB)1 Drug is infused with precisely controlled low infusion rates that create a pressure gradient that displaces the brain extracellular fluid with infusate.2

DIPG is a malignant high grade brain tumour of children. The median survival is only 9 months1 and no systemic treatment to date has been effective.1 This is likely due to the fact that the majority of systemic therapies do not cross the BBB to achieve a therapeutic concentration within the tumour.1 CED overcomes these limitations and has the potential to achieve a therapeutic drug concentration within the tumour without causing any systemic toxicity.1

The unique surgical technology developed in our department, allows repeated infusions of drug without the need for further surgery. The challenges faced by pharmacy were to ensure that an appropriate policy and register was developed to ensure that all professionals involved in the handling, prescription, preparation and administration of carboplatin by CED are appropriately trained and informed, and that patients receiving this therapy are safe. This follows the Department of Health guidance on the safe administration of intrathecal chemotherapy.3 This also had to be reflected on the prescription chart that was designed specifically for CED. It was necessary to ensure that carboplatin was stable at differing concentrations in the diluent used, artificial cerebrospinal fluid, and to determine the shelf life.

Outcome CED of carboplatin has been administered to 8 patients (ages 4–12 years) under compassionate use.4Patients were infused with up to 9 cycles of carboplatin for two consecutive days at a concentration of 0.18 mg/ml which were well tolerated, with neurological side effects most commonly seen during the first cycles.4 The process of safe prescribing and administration of carboplatin administered by this novel method is the first of its kind worldwide, and has the potential to revolutionise the treatment of malignant brainstem tumours.

References

  1. Barua NU, Lowis SP, Woolley M, et al. Robot-guided convection-enhanced delivery of carboplatin for advanced brainstem glioma. Acta Neurochirurgica2013;155:1459–65.

  2. Bobo RH, Laske DW, Akbasak A, et al. Convection-enhanced delivery of macromolecules in the brain. Proc Natl AcadSci U S A1994;91:2076–80.

  3. Department of Health. HSC 2008/ 001 Updated national guidance on the safe administration of intrathecal chemotherapy2008.

  4. Singleton WGB, Barua N, Morgan J, et al. Multi-catheter intermittent convection enhanced delivery of carboplatin as a treatment for Diffuse Intrinsic Pontine Glioma (DIPG): Pre-clinical rationale and early clinical experience. Proceedings of the International Symposium of Paediatric Neurooncology (ISPNO), Neuro-Oncology June 2016;18:131.

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