Brain Tumor Res Treat.  2019 Oct;7(2):85-91. 10.14791/btrt.2019.7.e33.

Efficacy of Slow Rate Ventriculolumbar Perfusion Chemotherapy for Leptomeningeal Carcinomatosis: Interim Result of a Phase II Study

• Choi YH
• Gwak HS
• Joo J
• Kwon JW
• Shin SH
• Yoo H
• Lee JH
• Youn JH

• KMID: 2461180
• DOI: http://doi.org/10.14791/btrt.2019.7.e33

Abstract

BACKGROUND
To evaluate the efficacy of modified ventriculolumbar perfusion (VLP) chemotherapy with methotrexate on leptomeningeal carcinomatosis in terms of symptomatic response and side effects.
METHODS
Previous infusion rate of 20 mL/h was reduced to 15 mL/h for the purpose of decreasing constitutional side effects of VLP such as nausea/vomiting, insomnia and confusion. The primary outcome was the response rate of increased intracranial pressure (ICP), and the secondary outcome was the occurrence of side effects compared to previous 20 mL/h trial. This interim analysis to validate the reduced infusion rate is not to affect the original effect of VLP chemotherapy.
RESULTS
All forty-seven patients were enrolled including 22 patients with increased ICP. Thirteen patients out of these (59%) got normalized ICP after VLP chemotherapy. Moderate to severe (grade 2-3) confusion was observed in 3 patients (6%) and it was significantly reduced compared to those (23%) in the VLP 20 mL/h (p=0.017). Grade 2-3 nausea/vomiting was also reduced from 64% to 45% but failed to reach statistical significance (p=0.08). Median overall survival (OS) was 5.3 months (95% confidence interval, 3.55-7.05) and patients OS, who received maintenance VLP was significantly prolonged compared to patients who underwent induction VLP only (5.8 vs. 3.4 months, p=0.025).
CONCLUSION
VLP of reduced perfusion rate (15 mL/h) showed compatible control rate of increased ICP at this interim analysis. Decreased moderate to severe side effects and prolonged OS in patients received maintenance VLP encourage us to evaluate the effectiveness of this trial further.

Keyword

Intraventricular infusion; Chemotherapy; Leptomeningeal carcinomatosis; Methotrexate; Perfusion

MeSH Terms

Drug Therapy*
Humans
Infusions, Intraventricular
Intracranial Pressure
Meningeal Carcinomatosis*
Methotrexate
Perfusion*
Sleep Initiation and Maintenance Disorders
Methotrexate

Figure

• 

  Fig. 1 Treatment schema of ventriculolumbar MTX perfusion chemotherapy. MTX, methotrexate; CSF, cerebrospinal fluid; RI, radioisotope.

• 

  Fig. 2 Distribution of ICP. The distribution of individual patient's ICP (cm H2O) is shown before (left) and after (right) VLP chemotherapy with methotrexate. Gray scales differentiate individual patients. ICP, intracranial pressure; VLP, ventriculolumbar perfusion.

• 

  Fig. 3 Side effects during ventriculolumbar perfusion chemotherapy comparison of perfusion rate between 15 mL/h and 20 mL/h. A: Nausea and vomiting, moderate to severe Grade 2–3 (p=0.053). B: Sleep disturbance, moderate to severe Grade 2–3 (p=0.805). C: Confusion, moderate to severe Grade 2–3 (p=0.017).

• 

  Fig. 4 Kaplan-Meier overall survival curve in VLP 15 mL/h of (A) all 47 patients who were ‘intention-to-treat’ with VLP, (B) comparison of overall survival of patients who received maintenance VLP chemotherapy versus patients who underwent induction VLP chemotherapy only (p=0.025). VLP, ventriculolumbar perfusion.

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