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Japanese Journal of Clinical Oncology Advance Access originally published online on July 11, 2009
Japanese Journal of Clinical Oncology 2009 39(11):756-766; doi:10.1093/jjco/hyp074
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© The Author (2009). Published by Oxford University Press. All rights reserved

Elevating Blood Pressure as a Strategy to Increase Tumor-targeted Delivery of Macromolecular Drug SMANCS: Cases of Advanced Solid Tumors

Akinori Nagamitsu1, Khaled Greish2,3 and Hiroshi Maeda2,3

1 Kumamoto Hakuaikai Hospital
2 Faculty of Pharmaceutical Sciences, Sojo University
3 Biodynamics Research Laboratory, Regional Collaboration Research Center, Kumamoto University, Kumamoto, Japan

For reprints and all correspondence: Hiroshi Maeda, Faculty of Pharmaceutical Sciences, Sojo University, Ikeda 4-22-1, Kumamoto 860-0082, Japan. E-mail: hirmaeda{at}ph.sojo-u.ac.jp

Received February 17, 2009; accepted June 5, 2009

The purpose of this study is to evaluate the improved method of arterial infusion therapy of SMANCS (SX) with lipiodol under the angiotensin-induced hypertensive state for various difficult-to-treat solid tumors. Most patients were unresectable with no other therapeutic options, recurrence after resection, or patients do not respond to common treatments. The new method utilizes angiotensin II (AT) to induce hypertension (e.g. ~15–30 mmHg above norm) for 15–20 min. This method was successfully applied to metastatic liver cancer, cholangiocarcinoma, massive renal cell carcinoma, pancreatic and other abdominal solid cancers. This AT-induced hypertension resulted in remarkably enhanced tumor delivery accompanied by improved therapeutic response, and a shorter time to achieve 50% regression of tumor size with least toxicity. We demonstrated clinically herein improved therapy for various advanced solid tumors with SX by elevating the tumor blood flow selectively. This is the first clinical proof that modulations of vascular pathophysiology can uniquely accomplish enhanced tumor selective delivery of polymeric drugs and thus yielded better clinical outcome.

Key Words: tumor delivery • angiotensin-induced hypertension • SMANCS • intra-arterial infusion • metastatic liver cancer


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