Combined-modality radioimmunotherapy : synergistic effect of paclitaxel and additive effect of bevacizumab

Abstract Introduction This study was undertaken to investigate the effect of paclitaxel and bevacizumab on the therapeutic efficacy of90 Y-labeled B3 monoclonal antibody, directed against Ley antigen, for the treatment of Ley -positive A431 tumors implanted subcutaneously in the right hind flank of nude mice. Methods When the tumor size reached ∼200 mm3 , the mice received a single dose of intravenous (iv)90 Y-labeled B3 (60 μCi/150 μg or 100 μCi/150 μg B3), intraperitoneal paclitaxel (40 mg/kg) or iv bevacizumab (5 mg/kg) for monotherapy. To investigate the effect of combined therapies on survival, the mice were treated with two or three agents in the following combinations:90 Y-B3 on day 0 and paclitaxel on day 1; bevacizumab on −1 day and90 Y-B3 on day 0; bevacizumab on −1 day and paclitaxel on day 1; bevacizumab,90 Y-B3 and paclitaxel each at 1-day intervals. The mice with no treatment were used as a control. The tumor volume at 1000 mm3 was used as a surrogate end point of survival. Results Compared to control animals, paclitaxel delayed tumor growth with a significantly longer median survival time ( P