Devices, systems for localized delivery of a chemotherapy, hormonal therapy or targeted drug/biologic therapy to a target tissue area of an internal body organ of a patient. A catheter 10 forms a sealed treatment chamber in a natural lumen extending through the target tissue area. Air is purged from the chamber, which is then filled with a liquid drug solution for an adequate treatment session time, solution volume and drug concentration to saturate the target tissue area, thereby providing the treatment. The liquid drug solution may be circulated or recirculated through the chamber or maintained stationary therewithin. The drug may saturate the target tissue area and pass therethrough into the lymphatic system or interstitial space, which may serve as a reservoir of the drug for continued therapeutic treatment after withdrawal of the catheter. The chamber is evacuated at the end of the treatment session.