Anti-tumor Effects of Sorafenib Administered at Different Time Points in Combination with Transarterial Embolization in a Rabbit VX2 Liver Tumor Model

• Published in: Cardiovascular and interventional radiology Vol. 40; no. 11; pp. 1763 - 1768
• Main Authors: Tomozawa, Yuki, Nitta, Norihisa, Ohta, Shinichi, Watanabe, Shobu, Sonoda, Akinaga, Nitta-Seko, Ayumi, Tsuchiya, Keiko, Murata, Kiyoshi
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-11-2017; Springer Nature B.V
• Subjects: Animals; Anticancer properties; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Cardiology; Combined Modality Therapy; Disease Models, Animal; Drug Administration Schedule; Embolization; Embolization, Therapeutic - methods; Imaging; Inhibitor drugs; Laboratory Investigation; Liver; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - therapy; Medicine; Medicine & Public Health; Niacinamide - administration & dosage; Niacinamide - analogs & derivatives; Niacinamide - pharmacology; Nuclear Medicine; Phenylurea Compounds - administration & dosage; Phenylurea Compounds - pharmacology; Rabbits; Radiology; Targeted cancer therapy; Transplantation; Ultrasound; Combination therapy; Sorafenib; Transarterial embolization
• ISSN: 0174-1551; 1432-086X
• DOI: 10.1007/s00270-017-1719-9

Objective
To investigate the most suitable timing parameters when using sorafenib to enhance the anti-tumor effects of transarterial embolization (TAE) in a rabbit VX2 liver tumor model.
Materials and Methods
Twenty-five Japanese white rabbits were randomly assigned to five equal groups two weeks after VX2 tumor transplantation to the liver. We then performed the combination treatment with sorafenib and TAE in the according ways; Group 1 (TAE just before consecutive 7-day administration of sorafenib), Group 2 (TAE on second day of the administration period), Group 3 (TAE on fourth day of the administration period), and Group 4 (TAE after the administration period). Group 5 underwent TAE only. The anti-tumor effects were assessed by the tumor growth rates and by the immunohistochemical analysis of the density of intratumoral vessels.
Results
The tumor size increased by 103 ± 23% in Group 1, 126 ± 50% in Group 2, 177 ± 44% in Group 3 196 ± 78% in Group 4, and 211 ± 20% in Group 5. The difference between Group 1 and Group 5 and Group 2 and Group 5 was significant. The ratio of areas positive for CD31 in specimens was 2.06 ± 0.90% in Group 1, 1.86 ± 0.59% in Group 2, 3.51 ± 2.10% in Group 3, 3.67 ± 0.79% in Group 4, and 4.84 ± 0.81% in Group 5. The difference between Group 1 and Group 5, Group 2 and Group 5, and Group 2 and Group 4 was significant.
Conclusion
We suggest that the ideal time of TAE is prior to or early after commencement of sorafenib administration.