Intra-arterial chemotherapy with osmotic blood-brain barrier disruption for aggressive oligodendroglial tumors: Results of a phase i study

Daniel J. Guillaume, Nancy D. Doolittle, Seymur Gahramanov, Nancy A. Hedrick, Johnny B. Delashaw, Edward A. Neuwelt

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

OBJECTIVE: Refractory anaplastic oligodendroglioma and oligoastrocytoma tumors are challenging to treat. This trial primarily evaluated toxicity and estimated the maximum tolerated dose of intra-arterial (IA) melphalan, IA carboplatin, and intravenous (IV) etoposide phosphate in conjunction with blood-brain barrier disruption in these tumors. The secondary measure was efficacy. METHODS: Thirteen patients with temozolomide-refractory anaplastic oligodendroglioma (11 patients) or oligoastrocytoma (2 patients) underwent blood-brain barrier disruption with carboplatin (IA, 200 mg/m2/d), etoposide phosphate (IV, 200 mg/m2/d), and melphalan (IA, dose escalation) every 4 weeks, for up to 1 year. Patients underwent melphalan dose escalation (4, 8, 12, 16, and 20 mg/m2/d) until the maximum tolerated dose (1 level below that producing grade 4 toxicity) was determined. Toxicity and efficacy were assessed. RESULTS: Two of 4 patients receiving IA melphalan at 8 mg/m2/d developed grade 4 thrombocytopenia; thus, the melphalan maximum tolerated dose was 4 mg/m2/d. Adverse events included asymptomatic subintimal tear (1 patient) and grade 4 thrombocytopenia (3 patients). Two patients demonstrated complete response, 3 had partial responses, 5 demonstrated stable disease, and 3 progressed. Median overall progression-free survival was 11 months. Patients with complete or partial response demonstrated deletion of chromosomes 1p and 19q. In the 5 patients with stable disease, 2 demonstrated 1p and 19q deletion, and 3 demonstrated 19q deletion only. CONCLUSION: In patients with anaplastic oligodendroglioma or oligoastrocytoma tumors in whom temozolomide treatment has failed, osmotic blood-brain barrier disruption with IA carboplatin, IV etoposide phosphate, and IA melphalan (4 mg/m2/d for 2 days) shows acceptable toxicity and encouraging efficacy, especially in patients demonstrating 1p and/or 19q deletion.

Original languageEnglish (US)
Pages (from-to)48-58
Number of pages11
JournalNeurosurgery
Volume66
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • Anaplastic oligodendroglioma
  • Blood-brain barrier
  • Chemotherapy
  • Intra-arterial chemotherapy
  • Oligoastrocytoma
  • Oligodendroglial tumors

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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