Intra-arterial infusion chemotherapy with angiotensin-II for locally advanced and nonresectable pancreatic adenocarcinoma: further evaluation and prognostic implications

Ann Surg Oncol. 2003 Oct;10(8):927-34. doi: 10.1245/aso.2003.10.021.

Abstract

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.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Angiotensin II / administration & dosage
  • Angiotensin II / therapeutic use*
  • Chi-Square Distribution
  • Female
  • Humans
  • Infusions, Intra-Arterial
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Statistics, Nonparametric
  • Survival Analysis
  • Vasoconstrictor Agents / administration & dosage
  • Vasoconstrictor Agents / therapeutic use*

Substances

  • Vasoconstrictor Agents
  • Angiotensin II
  • Methotrexate