Therapeutic agents for treatment of established metastases and inhibitors of metastatic spread: preclinical and clinical progress.

This article reviews recently described agents for the treatment of established metastases or inhibitors of metastatic spread. Recent progress in both preclinical models of experimental metastasis and clinical evaluation is highlighted. Where possible, distinctions are made between therapeutic agents for established metastatic tumors and those that merely interfere with the process of metastasis. The approaches emphasized include radiotherapy, cytotoxic chemotherapy, targeting the metastatic process and tumor metastases (adhesion, invasion, and angiogenesis), and modulation of the immune response, including chemoimmunotherapy. Emphasis has been placed on the necessity of using appropriate animal models of metastatic disease for the discovery and development of novel and effective antimetastatic therapeutic agents. Also addressed is the likelihood that future approaches to the metastasis problem will employ novel combined antimetastatic therapeutic modalities.