Intra-arterial infusion chemotherapy with angiotensin-II for locally advanced and nonresectable pancreatic adenocarcinoma: further evaluation and prognostic implications.
BACKGROUND
For locally advanced and nonresectable cancer of the pancreas, we performed intra-arterial infusion chemotherapy with angiotensin-II (AT-II). In our preliminary report, this treatment resulted in a median of 14 months of survival without objective adverse effects. This study was designed to clarify the prognostic factor in this chemotherapy by using a larger number of cases.


METHODS
For 32 patients, intra-arterial chemotherapy was performed: 1 or 2 catheters were intraoperatively placed into the pancreas-supplying arteries. The tissue blood flow and its change by AT-II infusion were determined. For intra-arterial chemotherapy, a mixture of methotrexate (50 or 100 mg/m(2)) and AT-II (.4 microg/kg/hour) was repeatedly infused from the catheter, mainly at our outpatient clinic.


RESULTS
With our intra-arterial chemotherapy, the median survival period was 13 months. The median survival period was 19 months in patients without coexisting pancreatitis but was only 9 months in those with it (P =.0003). The presence or absence of coexisting fibrosis in the neighboring uninvolved pancreas offered the only prognostic indicator. The blood flow in cancerous tissue was increased during AT-II infusion, and this was characteristic in the patients whose neighboring uninvolved pancreas had normal parenchyma (nonatrophic) or higher blood flow before AT-II infusion.


CONCLUSIONS
Because the AT-II infusion played a role in shifting the blood flow from the surrounding uninvolved pancreas to the cancer tissues, we can speculate that cancer tissues might have thereby received a higher dose of anticancer drugs if the surrounding uninvolved pancreas had been nonfibrotic and more rich in tissue blood flow.
Ohigashi
Hiroaki
H
Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. oohigasi-hi@mc.pref.osaka.jp
Ishikawa
Osamu
O
Yokayama
Shigekazu
S
Sasaki
Yo
Y
Yamada
Terumasa
T
Imaoka
Shingi
S
Nakaizumi
Akihiko
A
Uehara
Hiroyuki
H
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000008:administration & dosage / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D008727:Methotrexate