Enhanced antitumor effect of tirapazamine delivered intraperitoneally to VX2 liver tumor-bearing rabbits subjected to transarterial hepatic embolization

Cardiovasc Intervent Radiol. 2011 Dec;34(6):1272-7. doi: 10.1007/s00270-011-0156-4. Epub 2011 Apr 9.

Abstract

Purpose: We evaluated the effects of the combination of Tirapazamine (TPZ), activated preferentially under hypoxic conditions, and gelatin microspheres (GMS) on the tumor growth ratio in rabbits.

Methods: We assigned 20 liver tumor-bearing Japanese white rabbits to 4 equal groups. Group 1 received 1 ml of saline intra-arterially (i.a.) and 20 ml of saline intraperitoneally (i.p.; saline group). Group 2 was injected with GMS i.a. and 20 ml saline i.p. (GMS group). Group 3 received 1 ml of saline i.a. and 300 mg/m(2) of TPZ i.p. (TPZ group), and group 4 was treated with GMS i.a. and 300 mg/m(2) of TPZ i.p. (GMS + TPZ group). The infusion of GMS was stopped when the blood flow stagnated. Before and 7 days after treatment, the liver tumor volumes were measured as the total number of pixels on 0.3Tesla (T) magnetic resonance imaging (MRI) scans.

Results: The tumor growth ratio (mean ± standard deviation) of the saline, GMS, TPZ, and GMS + TPZ groups was 519.15 ± 93.78, 279.24 ± 91.83, 369.78 ± 95.73, and 119.87 ± 17.62, respectively. The difference between the GMS + TPZ group and the other groups was statistically significant (P < 0.05).

Conclusions: Our results show that the combination of TPZ i.p. and GMS i.a. enhanced the antitumor effect of TPZ. This procedure may represent a new alternative treatment for patients with hepatic cell carcinoma.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Hepatocellular / therapy*
  • Liver Neoplasms, Experimental / therapy*
  • Magnetic Resonance Imaging
  • Microspheres
  • Rabbits
  • Tirapazamine
  • Triazines / administration & dosage
  • Triazines / pharmacology*

Substances

  • Antineoplastic Agents
  • Triazines
  • Tirapazamine