Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy.
We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of (131)I-A7, an IgG1 anti-colorectal monoclonal antibody, or (131)I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation ( n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice ( n=8) ( P<0.05). (131)I-A7 RIT displayed a marked therapeutic effect ( n=8) ( P<0.001); however, all animals eventually died due to metastases by 99 days. The combined regimen of (131)I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy ( n=10) ( P<0.05); three mice survived the entire 160-day observation period. The combination of antiangiogenic therapy and (131)I-HPMS-1 RIT failed to provide an appreciable benefit ( n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases.
Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan. kinuya@med.kanazawa-u.ac.jp
Seigo
S
Kinuya
Kunihiko
K
Yokoyama
Kiyoshi
K
Koshida
Hirofumi
H
Mori
Kazuhiro
K
Shiba
Naoto
N
Watanabe
Noriyuki
N
Shuke
Jingming
J
Bai
Takatoshi
T
Michigishi
Norihisa
N
Tonami
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000628:therapy; D003131:Combined Modality Therapy / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A