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/m2) and AT-II (.4 μg/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.
Arbuck S. Overview of chemotherapy for pancreatic cancer. Int J Pancreatol 1990;7:209–22.PubMedGoogle Scholar
Rothman H, Cantrell JE Jr, Lokich J, et al. Continuous infusion 5-fluorouracil plus weekly cisplatin for pancreatic carcinoma. A Mid-Atlantic Oncology Program study. Cancer 1991;68:264–8.CrossRefPubMedGoogle Scholar
Rougier P, Zarba JJ, Ducreux M, et al. Phase II study of cisplatin and 120-hour continuous infusion of 5-fluorouracil in patients with advanced pancreatic adenocarcinoma. Ann Oncol 1993;4:333–6.CrossRefPubMedGoogle Scholar
Hansen R, Quebbeman E, Ritch P, Chitambar C, Anderson T. Continuous 5-fluorouracil (5FU) infusion in carcinoma of the pancreas: a phase II study. Am J Med Sci 1988;295:91–3.CrossRefPubMedGoogle Scholar
Oster MW, Gray R, Panasci L, Perry MC. Chemotherapy for advanced pancreatic cancer. A comparison of 5-fluorouracil, adriamycin, and mitomycin (FAM) with 5-fluorouracil, streptozotocin, and mitomycin (FSM). Cancer 1986;57:29–33.CrossRefPubMedGoogle Scholar
Ryan DP, Kulke MH, Fuchs CS, et al. A phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic carcinoma. Cancer 2002;94:97–103.CrossRefPubMedGoogle Scholar
Nguyen TD, Theobald S, Rougier P, et al. Simultaneous high-dose external irradiation and daily cisplatin in unresectable, non-metastatic adenocarcinoma of the pancreas: a phase I-II study. Radiother Oncol 1997;45:129–32.CrossRefPubMedGoogle Scholar
Ardalan B, Ucar A, Reddy R, et al. Phase I trial of low dose N-phosphonacetyl-l-aspartic acid and high dose 5-fluorouracil administered concomitantly with radiation therapy for unresectable localized adenocarcinoma of the pancreas. Cancer 1994;74:1869–73.CrossRefPubMedGoogle Scholar
Thomas CR Jr, Weiden PL, Traverso LW, Thompson T. Concomitant intraarterial cisplatin, intravenous 5-flourouracil, and split-course radiation therapy for locally advanced unresectable pancreatic adenocarcinoma: a phase II study of the Puget Sound Oncology Consortium (PSOC-703). Am J Clin Oncol 1997;20:161–5.CrossRefPubMedGoogle Scholar
Crane CH, Abbruzzese JL, Evans DB, et al. Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer? Int J Radiat Oncol Biol Phys 2002;52:1293–302.CrossRefPubMedGoogle Scholar
Colucci G, Giuliani F, Gebbia V, et al. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell’Italia Meridionale. Cancer 2002;94:902–10.CrossRefPubMedGoogle Scholar
Gazet JC, Smith R. Intra-arterial chemotherapy for patients with inoperable carcinoma of the pancreas. Proc R Soc Med 1974;67:1182–3.PubMedCentralPubMedGoogle Scholar
Hafstroem L, Ihse I, Joensson P, Lunderquist A, Stridbeck H. Intraarterial 5-FU infusion with or without oral testolactone treatment in irresectable pancreatic cancer. Acta Chir Scand 1980;146:445–8.Google Scholar
McCracken JD, Olson M, Cruz AB, Leichman L, Oishi N. Radiation therapy combined with intra-arterial 5-FU chemotherapy for treatment of localized adenocarcinoma of the pancreas. Cancer Treat Rep 1982;66:549–51.PubMedGoogle Scholar
Smith L, Gazet J. Intra-arterial chemotherapy for patients with inoperable carcinoma of the pancreas. Ann R Coll Surg Engl 1980;62:208–12.Google Scholar
Theodors A, Bukowski R, Hewlett J, Livinfston R, Weick J. Intermittent regional infusion of chemotherapy for pancreatic adenocarcinoma. Am J Clin Oncol 1982;5:555–8.CrossRefPubMedGoogle Scholar
Ishida H, Makino T, Kobayashi M, Tsuneoka K. Laparoscopic measurement of pancreatic blood flow. Endoscopy 1983;15:107–10.CrossRefPubMedGoogle Scholar
Ohigashi H, Ishikawa O, Nakamori S, et al. Evaluation of intra-arterial infusion chemotherapy and radical pancreatectomy for patients with locally advanced pancreatic cancer. Jpn J Cancer Chemother 1993;20:1672–5.Google Scholar
Burris HA III, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15:2403–13.CrossRefGoogle Scholar
Ohigashi H, Ishikawa O, Sasaki Y, Imaoka S, Iwanaga T. Pancreas cancer: arterial infusion chemotherapy for advanced pancreatic cancer Taguchi T Eds. Arterial Infusion Chemotherapy: Revised and Updated Edition. Tokyo:: Japanese Journal of Cancer and Chemotherapy Publications Inc, 1994: 416–26.Google Scholar
Noguchi S, Miyauchi K, Nishizawa Y, et al. Augmentation of anticancer effect with angiotensin II in intraarterial infusion chemotherapy for breast carcinoma. Cancer 1988;62:467–73.CrossRefPubMedGoogle Scholar
Sasaki Y, Imaoka S, Hasegawa Y, et al. Changes in distribution of blood flow induced by intra-arterial infusion of angiotensin II in human hepatic cancer. Cancer 1985;55:311–6.CrossRefPubMedGoogle Scholar
Hemingway D, Angerson WJ, Anderson JH, Goldberg JA, McArdle CS, Cooke TG. Monitoring blood flow to colorectal liver metastases using laser Doppler flowmetry: the effect of angiotensin II. Br J Cancer 1992;66:958–60.CrossRefPubMedCentralPubMedGoogle Scholar
Sasaki Y, Imaoka S, Hasegawa Y, et al. Distribution of arterial blood flow in human hepatic cancer during chemotherapy: examination by short-lived 81mKr. Surgery 1985;97:409–14.PubMedGoogle Scholar
Homma H, Doi T, Mezawa S, et al. A novel arterial infusion chemotherapy for the treatment of patients with advanced pancreatic carcinoma after vascular supply distribution via superselective embolization. Cancer 2000;89:303–13.CrossRefPubMedGoogle Scholar
Urbach DR, Swanstrom LL, Hansen PD. The effect of laparoscopy on survival in pancreatic cancer. Arch Surg 2002;137:191–9.CrossRefPubMedGoogle Scholar