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J Neurooncol. 2015 Oct;125(1):133-41. doi: 10.1007/s11060-015-1878-y. Epub 2015 Aug 9.

Methotrexate administration directly into the fourth ventricle in children with malignant fourth ventricular brain tumors: a pilot clinical trial.

Author information

1
Division of Pediatric Neurosurgery, Departments of Pediatric Surgery and Neurosurgery, University of Texas Health Science Center at Houston and Mischer Neuroscience Center, 6431 Fannin Street, MSB 5.144, Houston, TX, 77030, USA. david.i.sandberg@uth.tmc.edu.
2
Divisions of Neurosurgery and Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX, USA. david.i.sandberg@uth.tmc.edu.
3
Division of Pediatrics, Unit 87, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
4
Division of Neurosurgery, Department of Pediatric Surgery, University of Texas Health Science Center at Houston, 6431 Fannin St., MSB 5.146, Houston, TX, 77030, USA.
5
Unit 1482, Department of Diagnostic Imaging, Section of Neuroradiology, FCT 16.5020, University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
6
Unit 85, Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
7
Unit 1472, Department of Imaging Physics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
8
Department of Diagnostic & Interventional Imaging, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 2.130B, Houston, TX, 77030, USA.
9
Ziopharm Oncology Inc., 1 First Avenue; Parris Building, #34, Navy Yard Plaza, Boston, MA, 02129, USA.
10
Department of Biostatistics, Office FCT 4.614, MD Anderson Cancer Center, Houston, TX, 77230-1402, USA.

Abstract

We hypothesize that chemotherapy can be safely administered directly into the fourth ventricle to treat recurrent malignant brain tumors in children. For the first time in humans, methotrexate was infused into the fourth ventricle in children with recurrent, malignant brain tumors. A catheter was surgically placed into the fourth ventricle and attached to a ventricular access device. Cerebrospinal fluid (CSF) flow was confirmed by CINE MRI postoperatively. Each cycle consisted of 4 consecutive daily methotrexate infusions (2 milligrams). Disease response was monitored with serial MRI scans and CSF cytologic analysis. Trough CSF methotrexate levels were sampled. Five patients (3 with medulloblastoma and 2 with ependymoma) received 18, 18, 12, 9, and 3 cycles, respectively. There were no serious adverse events or new neurological deficits attributed to methotrexate. Two additional enrolled patients were withdrawn prior to planned infusions due to rapid disease progression. Median serum methotrexate level 4 h after infusion was 0.04 µmol/L. Range was 0.02-0.13 µmol/L. Median trough CSF methotrexate level 24 h after infusion was 3.18 µmol/L (range 0.53-212.36 µmol/L). All three patients with medulloblastoma had partial response or stable disease until one patient had progressive disease after cycle 18. Both patients with ependymoma had progressive disease after 9 and 3 cycles, respectively. Low-dose methotrexate can be infused into the fourth ventricle without causing neurological toxicity. Some patients with recurrent medulloblastoma experience a beneficial anti-tumor effect both within the fourth ventricle and at distant sites.

KEYWORDS:

Ependymoma; Fourth ventricle; Intraventricular chemotherapy; Medulloblastoma; Methotrexate

PMID:
26255071
PMCID:
PMC4592494
DOI:
10.1007/s11060-015-1878-y
[Indexed for MEDLINE]
Free PMC Article

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