Abstract
Background
Locoregional intra-arterial (i.a.) chemotherapy may provide high levels of cytostatic concentrations within the tumour and, simultaneously, a low rate of systemic side effects compared with systemic administration of anti-neoplastic drugs. In addition, this may lead to an increase of tumour response rate and prolongation of survival time. The aim of the study was (1) to evaluate the benefit of an i.a. infusion of cytostatic drugs via the coeliac trunk on tumour response rate and survival time, (2) to elucidate problems and risks, and finally (3) to achieve an improvement of overall therapeutic management in pancreatic carcinoma.
Patients and methods
In 22 patients (12 female; 10 male; mean age 57.1 years) with locally advanced pancreatic carcinoma, which was confirmed by histopathology, i.a. chemotherapy was administered. Through a catheter, which was inserted via the femoral artery by the Seldinger technique and placed with the tip in the coeliac trunk, two different drug combinations were given. Group A (n=12) were given a bolus injection of a mixture (chemo-occlusion) consisting of amilomer (Spherex) and epirubicin (Farmorubicin) followed by short-time infusion of folic acid and 24-h infusion of 5-FU. Group B (n=10) were given treatment over 5 days: mitoxantrone (Novantrone, day [d] 1), 5-FU and folic acid (Haemato-folin, d 2–4), and cisplatin (d 5). Treatment was repeated in both groups every 4 weeks. Tumour response was assessed by computed tomography every 8 weeks.
Results
In group A, there was one complete and one partial remission, resulting in a remission rate of 16.6%. Two patients showed stable disease, while in two-thirds of the patients (n=8), progressive disease was found. Median survival time was 3 months; 1-year survival rate was 33.3% (4 of 12 patients). In group B, again, one complete and one partial remission were observed (remission rate 20%). In three cases, stable disease, and in 50% of patients (n=5), progressive disease, were documented. Median survival was 7.0 months; 1-year survival rate was 20% (2 of 10 patients). If both groups were compared, there was no difference in survival. In addition, no prolongation of survival time was found in comparison with patients of a historical study group treated with established systemic chemotherapy using gemcitabine monotherapy (n=28; median survival time 9 months). Though a tendency for poorer outcome of i.a. chemotherapy was seen when the Kaplan–Meier curves of survival were compared, this difference was not statistically significant (log rank test, P=0.08).
Conclusion
Despite conceptual and pharmacokinetic advantages of locoregional i.a. chemotherapy, better outcome with regard to tumour response rate and survival time could not be found. I.a. chemotherapy is, therefore, still an experimental treatment option in pancreatic carcinoma and can, currently, not be recommended for routine use.
Similar content being viewed by others
References
Matthias M, Wolff H (1987) Problems of antineoplastic chemotherapy of pancreatic cancer. Zentralbl Chir 112:1322–1336
Collins JM (1984) Pharmacologic rationale for regional drug delivery. J Clin Oncol 2:498–504
Schalhorn A, Kuhl M (1995) Pharmacology of regional chemotherapy of colorectal liver metastases. Zentralbl Chir 120:764–768
Meta-Analysis Group (1996) Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. J Natl Cancer Inst 88:252–258
Aigner KR, Santinami M (1994) Regional therapy for pelvic, rectal and urologic tumors: has it any role? Reg Cancer Treat 1:1
Aigner KR, Thiem N (1994) Regional chemotherapy for recurrent breast cancer—the effect of different techniques of drug administration on tumour response. Reg Cancer Treat 7:127–131
Itin AB (1972) Regional intra-arterial chemotherapy of cancer of the pancreas. Khirurgiia (Mosk) 148:22–25
Aigner KR, Müller H, Bassermann R (1990) Intra-arterial chemotherapy with MMC, CDDP and 5-FU for nonresectable pancreatic cancer—a phase II study. Reg Cancer Treat 3:1–6
Gansauge F, Link KH, Rilinger N, Kunz R, Beger HG (1995) Regional chemotherapy in advanced pancreatic carcinoma. Med Klin 90:501–505
Link KH, Formentini A, Gansauge F, Papachristov E, Beger HG (1997) Regional celiac artery infusion as adjuvant treatment after pancreatic cancer resection. Digestion 58:529–532
Link KH, Gansauge F, Pillasch J, Rilinger N, Buchler M, Beger HG (1994) Regional treatment of advanced nonresectable and of resected pancreatic cancer via celiac axis infusion. Dig Surg 11:414–419
Aigner KR, Gailhofer S, Kopp S (1998) Regional versus systemic chemotherapy for advanced pancreatic cancer: a randomized study. Hepatogastroenterology 45:1125–1129
Storniolo AM, Enas NH, Brown CA, Voi M, Rothenberg ML, Schilsky R (1999) An investigational new drug treatment program for patients with gemcitabine: results for over 3,000 patients with pancreatic carcinoma. Cancer 85:1261–1268
Schalhorn A, Kuhl M (1992) Clinical pharmacokinetics of fluorouracil and folinic acid. Semin Oncol 19:82–92
Zeller WJ, Zur Hausen H (1995) Onkologie: Grundlagen-Diagnostik-Therapie-Entwicklungen. ecomed.- Losebl. 13[IV-3], 1–4. ecomed.- Losebl.-Ausg. NE, Landsberg/Lech (magazine article)
Gutman M, Abu-Abid S, Sorkine P, Inbar M, Lev D, Chen Z, Oron D, Chaitchik S, Klausner JM (1996) Regional perfusion with hemofiltration (chemofiltration) for the treatment of patients with regionally advanced cancer. Cancer 78:1125–1130
Shibuya K, Nagata Y, Itoh T, Okajima K, Murata R, Takagi T, Hiraoka M (1999) Transcatheter arterial infusion therapy in the treatment of advanced pancreatic cancer: a feasibility study. Cardiovasc Intervent Radiol 22:196–200
Grosso M, Zanon C, Zanon E, Corsico M, Gazzera C, Mancini A, Fava C (1997) The percutaneous placement of intra-arterial catheters with “reservoirs” for subcutaneous infusion. The technic and preliminary results. Radiol Med (Torino) 94:226–232
Tominaga M, Ku Y, Iwasaki T, Suzuki Y, Kuroda Y, Saitoh Y (1997) Pharmacological evaluation of portal venous isolation and charcoal haemoperfusion for high-dose intra-arterial chemotherapy of the pancreas. Br J Surg 84:1072–1076
Homma H, Doi T, Mezawa S (2000) A novel arterial infusion chemotherapy for the treatment of patients with advanced pancreatic carcinoma after vascular supply distribution via superselective embolization. Cancer 89:303–313
Muchmore JH, Carter RD, Preslan JE, George WJ (1996) Regional chemotherapy with hemofiltration: a rationale for a different treatment approach to advanced pancreatic cancer. Hepatogastroenterology 43:346–355
Muchmore JH, Preslan JE, George WJ (1996) Regional chemotherapy for inoperable pancreatic carcinoma. Cancer 78:664–673
Cantore M, Pederzoli P, Cornalba G, Fiorentini G, Guadagni S, Miserocchi L, Frassoldati A, Ceravolo C, Smerieri F, Muchmore JH (2000) Intra-arterial chemotherapy for unresectable pancreatic cancer. Ann Oncol 11:569–573
Ohigashi H, Ishikawa O, Imaoka S, Sasaki Y, Kabuto T, Kameyama M, Furukawa H, Hiratuka M, Nakamori S, Nakano H, Yasuda T, Iwanaga T (1996) A new method of intra-arterial regional chemotherapy with more selective drug delivery for locally advanced pancreatic cancer. Hepatogastroenterology 43:338–345
Hafstrom L, Ihse I, Jonsson PE, Lunderquist A, Stridbeck H (1980) Intraarterial 5-FU infusion with or without oral testolactone treatment in irresectable pancreatic cancer. Acta Chir Scand 146:445–448
Maurer CA, Borner MM, Lauffer J, Friess H, Z’graggen K, Triller J, Buchler MW (1998) Celiac axis infusion chemotherapy in advanced nonresectable pancreatic cancer. Int J Pancreatol 23:181–186
Theodors A, Bukowski RM, Hewlett JS, Livingston RB, Weick JK (1982) Intermittent regional infusion of chemotherapy for pancreatic adenocarcinoma. Phase I and II pilot study. Am J Clin Oncol 5:555–558
Adjei AA, Erlichman C (1999) A phase I trial of MTA and gemcitabine in patients with locally advanced or metastatic cancer. Semin Oncol 26:94–98
van Groeningen CJ (1999) Intravenous and intra-arterial chemotherapeutic possibilities in biliopancreatic cancer. Ann Oncol 10 [Suppl 4]:305–307
Lorenz M, Heinrich S, Staib-Sebler E, Kohne CH, Wils J, Nordlinger B, Encke A (2000) Regional chemotherapy in the treatment of advanced pancreatic cancer—is it relevant? Eur J Cancer 36:957–965
Stephens FO (1995) Induction (neo-adjuvant) chemotherapy: systemic and arterial delivery techniques and their clinical applications. Aust N Z J Surg 65:699–707
Klapdor R, Seutter E, Lang-Polckow EM, Reichle H, Hinrichs A (1999) Locoregional/systemic chemotherapy of locally advanced/metastasized pancreatic cancer with a combination of mitomycin-C and gemcitabine and simultaneous follow-up by imaging methods and tumor markers. Anticancer Res 19:2459–2469
Müller H (1997) Angio-genesis-inhibition and intra-arterial chemotherapy—a new modality treatment for advanced metastatic pancreatic carcinoma. Eur J Cancer 33 [Suppl 8]: 215–215
Acknowledgments
The authors are grateful to U. Schmidt, Ph.D., Department of Biometrics and Biostatistics, University Hospital, Otto von Guericke University at Magdeburg (Germany) for appropriate statistical advice.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Meyer, F., Grote, R., Lippert, H. et al. Marginal effects of regional intra-arterial chemotherapy as an alternative treatment option in advanced pancreatic carcinoma. Langenbecks Arch Surg 389, 32–39 (2004). https://doi.org/10.1007/s00423-003-0431-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00423-003-0431-1