Enhanced efficacy of radioimmunotherapy combined with systemic chemotherapy and local hyperthermia in xenograft model.
We previously found that the efficacy of radioimmunotherapy (RIT) with (131)I-A7, an IgG(1) against M(r) 45000 glycoprotein on colon cancer, was enhanced by local hyperthermia (HT) or chemotherapy with 5-fluorouracil (5-FU). In this study, we aimed to further enhance its efficacy by combining these three modalities. Human colon cancer xenografts (146 x 12 mm(3)) in Balb / c nu / nu female mice were treated with 9.25 MBq (131)I-A7 i.v. combined with HT (43 degrees C for 1 h) and 5-FU (30 mg / kg / day i.p. for 5 days). Tumor growth delay, (Tq(treated) - Tq(control) )/ Tq(control) where Tq is tumor quadrupling time, in mice treated with RIT + HT + 5-FU was improved to 12.7 from 5.90, 7.55 and 10.1 with RIT alone, RIT + 5-FU and RIT + HT, respectively. Complete response was observed in 4 out of 8 tumors with RIT + HT + 5-FU and 3 out of 10 with RIT + HT. No tumor showed complete response with RIT + 5-FU or RIT alone. 5-FU slightly increased myelotoxicity of RIT, but HT did not affect it. Body weight loss was not enhanced by the combination. These results indicate that the combination of three modalities is a feasible approach to enhance the antitumor efficacy of RIT without serious increase of toxicity.
Kinuya
S
S
Department of Nuclear Medicine, Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa 920-8640, Japan. kinuya@med. kanazawa-u.ac.jp.
Yokoyama
K
K
Konishi
S
S
Hiramatsu
T
T
Watanabe
N
N
Shuke
N
N
Aburano
T
T
Takayama
T
T
Michigishi
T
T
Tonami
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001835:Body Weight; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006979:Hyperthermia, Induced / Q000379:methods*; D007074:Immunoglobulin G / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy*; D016499:Radioimmunotherapy / Q000379:methods*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D007074:Immunoglobulin G; D005472:Fluorouracil