Enhanced efficacy of radioimmunotherapy combined with systemic chemotherapy and local hyperthermia in xenograft model

We previously found that the efficacy of radioimmunotherapy (RIT) with I-13 1-A7, an IgG(1) against M-r 45000 glycoprotein on colon cancer, was enhance d by local hyperthermia (HT) or chemotherapy with 5-fluorouracil (5-FU), In this study, we aimed to further enhance its efficacy by combining these th ree modalities. Human colon cancer xenografts (146+/-12 mm(3)) in Balb/c nu /nu female mice were treated with 9.25 MBq (131)r-A7 i.v. combined with HT (43 degrees C for I h) and 5-FU (30 mg/kg/day i.p. for 5 days). Tumor growt h delay, (Tq(treated)-Tq(control))/Tq(control) where Tq is tumor quadruplin g time, in mice treated with RIT+HT+5-FU,vas improved to 12.7 from 5.90, 7. 55 and 10.1 with RIT alone, RIT+5-FU and RIT+HT, respectively, Complete res ponse was observed in 4 out of 8 tumors with RIT+HT+5-FU and 3 out of 10 wi th 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 tha t the combination of three modalities is a feasible approach to enhance the antitumor efficacy of RIT without serious increase of toxicity.