TY - JOUR
T1 - Intra-arterial chemotherapy with osmotic blood-brain barrier disruption for aggressive oligodendroglial tumors
T2 - Results of a phase i study
AU - Guillaume, Daniel J.
AU - Doolittle, Nancy D.
AU - Gahramanov, Seymur
AU - Hedrick, Nancy A.
AU - Delashaw, Johnny B.
AU - Neuwelt, Edward A.
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Anaplastic oligodendroglioma
KW - Blood-brain barrier
KW - Chemotherapy
KW - Intra-arterial chemotherapy
KW - Oligoastrocytoma
KW - Oligodendroglial tumors
UR - http://www.scopus.com/inward/record.url?scp=77249102549&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77249102549&partnerID=8YFLogxK
U2 - 10.1227/01.NEU.0000363152.37594.F7
DO - 10.1227/01.NEU.0000363152.37594.F7
M3 - Article
C2 - 20023537
AN - SCOPUS:77249102549
SN - 0148-396X
VL - 66
SP - 48
EP - 58
JO - Neurosurgery
JF - Neurosurgery
IS - 1
ER -
