Elevating blood pressure as a strategy to increase tumor-targeted delivery of macromolecular drug SMANCS: cases of advanced solid tumors.
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. approximately 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.
Nagamitsu
Akinori
A
Kumamoto Hakuaikai Hospital, Kumamoto, Japan.
Greish
Khaled
K
Maeda
Hiroshi
H
D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D018281:Cholangiocarcinoma / Q000188:drug therapy; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D007262:Infusions, Intravenous; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D008299:Maleic Anhydrides / Q000008:administration & dosage*; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D011137:Polystyrenes / Q000008:administration & dosage*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*; D009353:Zinostatin / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000970:Antineoplastic Agents; D008299:Maleic Anhydrides; D011137:Polystyrenes; D014662:Vasoconstrictor Agents; C035755:poly(maleic acid-styrene)neocarzinostatin; D000804:Angiotensin II; D009353:Zinostatin