BACKGROUND. We developed a new anti-cancer treatment, which is a combination of chemotherapeutic agents and low electric field. In the present study we investigated its efficacy against prostate metastatic transgenic adenocarcinoma of mice (TRAMP). METHODS. Mice with 5, 10, and 13 mm in diameter intracutaneous tumors received Low Electric field Cancer Treatment-Enhanced Chemotherapy (LEFCT-EC) with doxorubicin (10 mg/kg), and monitored for survival, and primary and metastatic tumors growth. RESULTS. The electric field increased the uptake of doxorubicin by TRAMP cells in vitro. In vivo use of LEFCT-EC reduced tumor size, prolonged survival, and cured 36-93 of the animals, dependent on treated tumor size. LEFCT-EC was more effective than surgery with or without chemotherapy. Part of the cured animals developed anti-tumor immunity and immunosuppression, significantly decreased the effectiveness of the treatment. CONCLUSION. Our results suggest that LEFCT-EC is an effective method for the destruction of metastatic prostate tumors. ? 2006 Wiley-Liss, Inc.