Enhanced Efficacy of Radioimmunotherapy Combined with Systemic Chemotherapy and Local Hyperthermia in Xenograft Model

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Abstract
We previously found that the efficacy of radioimmunotherapy (RIT) with 131I‐A7, an IgG1 against Mr 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±12 mm3) in Balb/c nu/nu female mice were treated with 9.25 MBq 131I‐A7 i.v. combined with HT (43°C for 1 h) and 5‐FU (30 mg/kg/day i.p. for 5 days). Tumor growth delay, (Tqtreated‐Tqcontrol)/Tqcontrol 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.