Should we offer the same moalities of therap

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Intra-Arterial Drug Administration

• Chemotherapy is injected into the artery that
  supplies blood into the tumor andsurrounding
  brain tissue
• Advantage
• During the injection the perfused tissue receives
  higher plasma concentration during the first
  passage through the circulation (increased AUCPL)
• Short duration of infusion (5-15 min) produces
  significantly higher plasma concentrations (Cmax)
  in humans

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Intra-Carotid Carboplatin
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Human Brain metastasis Platinum Levels
Treatment Plasma BAT
Tumor (ng Pt/ml)
(mg Pt/gr) (mg Pt/gr) IV DDP
7340 1022 2.34 0.5 4.68 0.6 (100
mg/m2) IA DDP 5172 717 2.10 0.6
8.5 1.3 (100 mg/m2) p value
NS NS
0.007
Nakagawa et al J Neuro-Oncology 1661-67, 1993
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Canine Brain MTX Levels(ng MTX/gr tissue)
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Osmotic Disruption of the BBB

• The principle features are
• Transient opening of the BBB induced byIA
  infusion of hyperosmolar solution(usually 1.4 M
  Mannitol)
• Followed by IA drug infusion (first pass
  advantage and bolus injection)
• BBBD has been explored in animals and humans with
  regard to brain tumors

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Osmotic BBB DisruptionRat Brain (I.V. Evans blue)
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Osmotic BBBD in Humans
Disruption of the Vertebral Artery Territory
Disruption of the LICA Territory
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Quantitative evaluation of BBBD
Excellent Disruption of the RICA territory
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MTX Penetration Into the Ventricular CSF Human
Studies
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Ventricular CSF Levels MTX
Carboplatin
r0.849 plt0.03
Vertebral
r0.627 plt0.029
ICA
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