Radiation therapy plus angiogenesis inhibition with bevacizumab: rationale and initial experience

Angiogenesis inhibition by monoclonal antibodies against vascular endothelial growth factor receptor (VEGFR) combined with cytotoxic chemotherapy has shown encouraging potential for improvement of cancer treatment. Several rationales exist for combining VEGFR antibodies with ionizing radiation, a primary curative cancer treatment, either in bimodal or trimodal fashion, i.e. with or without additional chemotherapy. This systematic review compares the results of preclinical and clinical studies published before December 2006. The combination of VEGFR inhibitors with irradiation in animal models consistently resulted in improved tumor growth delay (at least additive effects), despite different treatment schedules. Only one study evaluated tumor control dose (TCD)(50) as a measure of tumor cure (radiation dose yielding permanent local control in 50% of the tumors). Also in this setting, anti-VEGFR antibody treatment improved the outcome. Importantly, both radiotherapy schedule and sequence of the modalities in combined treatment may impact on the outcome. Hence, further preclinical studies examining these parameters need to be conducted. While preclinical research is ongoing, phase I and II clinical trials with bevacizumab, usually combined with radio- and chemotherapy, have been designed. Early results suggest that acute toxicity is acceptable, planned surgery after such treatment is feasible, and that further evaluation of such combined modality treatment is warranted.