Angiotensin II (AII) induced hypertension chemotherapy (IHC) for unresectable gastric cancer: with reference to resection after down staging

Abstract

Angiotensin II induced hypertension chemotherapy (IHC) is a drug delivery system for augmentation of anti-cancer effects on the experimental basis of the functional difference of microcirculation between tumor and normal tissue. Blood flow in tumor tissue increased selectively when the blood pressure was elevated by the infusion of angiotensin II. Two randomized controlled trials (RCT) for advanced gastric cancer using AFM regimen; a combination of adriamycin (ADM), 5-fluorouracil (5-FU), and mitomycin (MMC), showed increased response rate by IHC (response rate: IHC/non-IHC; 42.9% vs 10.5% in RCT-1, and 31.3% vs 6.7% in RCT-2, respectively). Toxicities were not different statistically between groups. In phase II for stage IVB gastric cancer patients (the criteria according to the General Rules of the Gastric Cancer Study of Japanese Research Society for Gastric Cancer), 5 complete response (CR) and 10 partial response (PR) (58%) were observed out of 26 unresectable cases without prior chemotherapy. Moreover, 5 of 15 responders could received curative gastrectomy and obtained conclusive down staging (19%). Here we discuss the role of enhancement of drug delivery for cancer chemotherapy on the basis of a series of clinical and experimental evidences.