A phase I trial of carboplatin administered by convection-enhanced delivery to patients with recurrent/progressive glioblastoma multiforme

Edward White, Alison Bienemann, Hannah Taylor, Kirsten Hopkins, Alison Cameron, Steven Gill

Research output: Contribution to journalArticle (Academic Journal)peer-review

38 Citations (Scopus)

Abstract

Glioblastoma multiforme (GBM) is the commonest primary malignant brain tumour in adults. Standard treatment comprises surgery, radiotherapy and chemotherapy; however this condition remains incurable as these tumours are highly invasive and involve critical areas of the brain making it impossible to remove them surgically or cure them with radiotherapy. In the majority of cases the tumour recurs within 2 to 3 cm of the original site of tumour resection. Furthermore, the blood-brain barrier profoundly limits the access of many systemically administered chemotherapeutics to the tumour. Convection-enhanced delivery (CED) is a promising technique of direct intracranial drug delivery involving the implantation of microcatheters into the brain. Carboplatin represents an ideal chemotherapy to administer using this technique as glioblastoma cells are highly sensitive to carboplatin in vitro at concentrations that are not toxic to normal brain in vivo. This protocol describes a single-centre phase I dose-escalation study of carboplatin administered by CED to patients with recurrent or progressive GBM despite full standard treatment. This trial will incorporate 6 cohorts of 3 patients each. Cohorts will be treated in a sequential manner with increasing doses of carboplatin, subject to dose-limiting toxicity not being observed. This protocol should facilitate the identification of the maximum-tolerated infused concentration of carboplatin by CED into the supratentorial brain. This should facilitate the safe application of this technique in a phase II trial, treating patients with GBM, as well as for the treatment of other forms of malignant brain tumours, including metastases.

Original languageEnglish
Pages (from-to)320-31
Number of pages12
JournalContemporary Clinical Trials
Volume33
Issue number2
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Adult
  • Antineoplastic Agents
  • Blood-Brain Barrier
  • Brain Neoplasms
  • Carboplatin
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems
  • Female
  • Follow-Up Studies
  • Glioblastoma
  • Humans
  • Male
  • Neoplasm Recurrence, Local
  • Treatment Outcome

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