Methods and pharmaceuticals for inhibiting or preventing metastasis formation in animals, including humans, having primary tumors, through the administration of phosphorothioates including their thiol and disulfide metabolites are disclosed. These compounds stimulate angiostatin levels, inhibit matrix metalloproteinases (MMPs), and stimulate manganese superoxidase dismutase (MnSOD). Phosphorothioates, of which amifostine is an example, can be administered as a combination therapy with traditional cancer therapies, including chemotherapy, radiotherapy, surgery, immunotherapy, hormone therapy and gene-therapy. Inhibition or prevention of metastasis by phosphorothioates is independent of tumor type, including adenocarcinomas and sarcomas.