Our preclinical in vivo investigations were aimed to evaluate the potential of selectively targeting the tumour vasculature as an additional anti-cancer strategy. Using a clinical angiography method and the tumour growth delay assay, the efficacy of the vascular targeting compound combretastatin A-4 phosphate was demonstrated in rat rhabdomyosarcomas: specifically, an inverse efficacy as compared to radio- or chemotherapy was measured when comparing small and large tumours. The combination of this vascular targeting compound with ionising radiation indicated, depending on the timing and the sequence, a potential benefit. Within the limits of our experiments, no significant increase in tumour growth delay was measured when TNP-470 anti-angiogenesis was given after the combretastatin A-4 phosphate treatment. The use of the vascular targeting agent did advance the in vivo application of a non-apathogenic anaerobe Clostridium transfer system of therapeutic proteins. A strong improvement of the selective expression of cytosine deaminase in the tumour microenvironment was observed, even with very small tumours. In summary, the present preclinical results demonstrate several advantages from the introduction of vascular targeting next to classical and novel anti-cancer therapies.