Abstract
The aim of the study was to evaluate the effectiveness and safety of a combined treatment modality including systemic chemotherapy with 5-fluorouracil (FU), leucovorin, cisplatin and external beam radiotherapy in patients with locally advanced pancreatic cancer. Systemic chemotherapy consisted of FU 400 mg m–2and leucovorin 20 mgm–2both given as intravenous bolus injection on days 1–4, plus cisplatin 20 mgm–2administered as 90-min infusion on days 1–4. Treatment courses were repeated every 4 weeks × 6 unless prior evidence of progressive disease. Radiation therapy using megavolt irradiation of ≥ 6 MV photons with a 3- or 4-field technique was delivered during the second and third chemotherapy course, that was reduced in dose by 25%. Between October 1994 and July 1996, a total of 38 patients were entered onto this trial, all of whom were assessable for toxicity and survival. Eighteen of these (47%) had objective remissions to combined radiochemotherapy, including four CR (11%), 13 (34%) had stable disease and seven patients (18%) showed tumour progression during treatment. The median progression-free interval of the entire study population was 10 months (range 3–32), and median overall survival was 14.0 months (range 3–45+ months); 53% of all patients were alive at 12 months, and 18% of patients were alive at 24 months respectively. Severe haematological side-effects comprised neutropenia in 18%, thrombocytopenia in 8% and anaemia in 11%. The most frequent non-haematological side-effects were nausea/vomiting (WHO grade 3: 18%), and diarrhoea (grade 3: 13%). This combined radiochemotherapy regimen was tolerable and effective in patients with locally advanced pancreatic cancer. Since therapeutic results, in fact, compare favourably with other series, including surgical treatment of potentially resectable tumours, further evaluation of combined treatment modalities in the neoadjuvant setting seems warranted. © 2000 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Andre T, Lotz JP, Bouleuc C, Azzouzi K, Houry S, Hannoun L, See J, Esteso A, Avenin D and Izrael V (1996) Phase II trial of 5-fluorouracil, leucovorin and cisplatin for treatment of advanced pancreatic adenocarcinoma. Ann Oncol 7: 173–178
BMDP Statistical Software (1985). BMDP Statistical Software Manual, University of California Press: Berkeley, CA
Bruckner HW, Crown J, McKenna A and Hart R (1988) Leucovorin and 5-fluorouracil as a treatment for disseminated cancer of the pancreas and unknown primary tumors. Cancer Res 48: 5570–5572
Byfield JE, Chan PYM and Seagren S (1974) Radiosensitization by 5-fluorouracil (5-FU): molecular and clinical scheduling implications. Proc Am Assoc Cancer Res 18: 74 (abstract)
Crown J, Caspers ES, Botet J, Murray P and Kelsen DP (1991) Lack of efficacy of high-dose leucovorin and fluorouracil in patients with advanced pancreatic. J Clin Oncol 9: 1682–1686
De Caprio JA, Arbuck SG and Mayer RJ (1989) Phase II study of weekly 5-fluorouracil (5-FU) and folinic acid (FA) in previosly untreated patients with unresectable measurable pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 8: 100, (abstract)
Dreyfuss AI, Clark JR, Wright JE, Norris CM, Busse PM, Lucarini JW, Fallon BG, Casey D, Anderson JW and Klein R (1990) Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck. Ann Intern Med 112: 167–172
Evans DB, Abbruzzese J, Lee J, Cleary K and Rich T (1994) Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Proc Am Soc Clin Oncol 13: 226 (abstract)
Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sobin LH and Yarbro JW (eds) (1997) Exocrine Pancreas. AJCC Cancer Staging Manual, 5th Edn, pp. 121–126. Lippincott-Raven: Philadelphia
Forastiere AA, Orringer MB, Perez-Tamayo C, Urba SG, Husted S, Takasugi BJ and Zahurak M (1990) Concurrent chemotherapy and radiation therapy followed by transhiatal esophagus. J Clin Oncol 8: 119–127
Gastrointestinal Tumor Study Group (1979) A multi-institutional comparative trial of radiation therapy alone and in combination with 5-FU for locally unresectable pancreatic cancer. Am Surg 189: 205–211
Gastrointestinal Tumor Study Group (1987) Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 59: 2006–2010
Gastrointestinal Tumor Study Group (1988) Treatment of locally unresectable carcinoma of the pancreas: comparison of combined modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst 80: 751–755
Griffin JF, Smalley SR, Jewell W, Paradelo JC, Reymond RD, Hassanein RE and Evans RG (1990) Patterns of failure after curative resection of pancreatic carcinoma. Cancer 66: 56–61
Gudjonsson B (1995) Critical analysis of costs, results of resection, and the need for standardized reporting. J Am Coll Surg 181: 483–503
Gralla RJ (1988) Preoperative and adjuvant chemotherapy in non small cell lung cancer. Semin Oncol 15: 8–12
Hart L, Chua C and Brophy L (1989) Salvage chemotherapy for metastatic breast carcinoma using cisplatin, fluorouracil and leucovorin: a phase I/II study. Proc Am Soc Clin Oncol 8: 43 (abstract)
Hoffman JP, Lipsitz S, Pisansky T, Weese JL, Solin L and Benson AB (1998) Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group study. J Clin Oncol 16: 317–323
Hörmann K (1996) Neoadjuvante Therapiekonzepte. Onkologie 19: 81–93
Kamthan AG, Morris JC, Dalton J, Mandeli JP, Chessner MR, Leben D, Cooperman A and Bruckner HW (1997) Combined modality therapy for stage II and stage III pancreatic carcinoma. J Clin Oncol 15: 2920–2927
Kaplan EL and Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481
Klaassen DJ, MacIntyre JM, Catton GE, Engstrom PF and Moertel CG (1985) Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent maintenance 5-fluorouracil – an Eastern Cooperative Oncology Group study. J Clin Oncol 3: 373–378
Komaki R, Wadlers S, Peters T, Byhardt RW, Order S, Gallagher MJ, Herskovic A and Pederson J (1992) High-dose local irradiation plus prophylactic hepatic irradiation and chemotherapy for inoperable adenocarcinoma of the pancreas. Cancer 69: 2807–2812
Moertel CG, Gunderson LL, Mailliard JA, McKenna PJ, Martenson JA, Burch PA and Cha SS (1994) Early evaluation of combined fluorouracil and leucovorin as radiation enhancer for locally unresectable, residual, or recurrent gastrointestinal carcinoma. J Clin Oncol 12: 21–27
Moertel CG, Frytak S, Hahn RG, O’Connell MJ, Reitemeier RJ, Rubin J, Schutt AJ, Weiland LH, Childs DS, Holbrook MA, Lavin PT, Livstone E, Spiro H, Knowlton A, Kalser M, Barkin J, Lessner H, Mann-Kaplan R, Ramming K, Douglas HO, Thomas P, Nave H, Bateman J, Lokich J, Brooks J, Chaffey J, Corson JM, Zamcheck N and Novak JW (1981) Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation +5-fluorouracil. Cancer 48: 1705–1710
Mohiuddin M, Regine WF, Stevens J, Rosato F, Barbot D, Biermann W and Cantor R (1995) Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas. J Clin Oncol 13: 2764–2768
Nagai H, Kuroda A and Morioka Y (1986) Lymphatic and local spread of T1 and T2 pancreatic cancer. Ann Surg 204: 65–71
Nakyajima Y, Miyainoto T and Tanabes M (1979) Enhancement of mamillian cell killing by 5-fluorouracil in combination with X-rays. Cancer Res 135: 185–206
Nicolson M, Webb A, Cunningham D, Norman A, O'Brien M, Hill A and Hickish T (1995) Cisplatin and protracted venous infusion 5-fluorouracil (CF) – good symptom relief with low toxicity in advanced pancreatic carcinoma. Ann Oncol 6: 801–804
Parker SL, Tong T, Bolden S and Wingo PA (1996) Cancer statistics. CA Cancer J Clin 46: 5–27
Popescu RA and Cunningham D (1997) Chemotherapy for advanced pancreatic cancer – some light at the end of the tunnel?. Ann Oncol 8: 415–416
Prott FJ, Schönekaes K, Preusser P, Ostkamp K, Wagner W, Micke O, Pötter R, Sulkowski U, Rübe C, Berns T and Willich N (1997) Combined modality treatment with accelerated radiotherapy and chemotherapy in patients with locally advanced inoperable carcinoma of the pancreas: results of a feasibility study. Br J Cancer 75: 597–601
Rothman H, Cantrell JE, Lokich J, Difino S, Harvey J, Ahlgren J and Fryer J (1991) Continuous infusion 5-fluorouracil plus weekly cisplatin for pancreatic carcinoma: a Mid-Atlantic Oncology Program study. Cancer 68: 264–268
Scheithauer W, Depisch D and Kornek G (1994) Randomized comparison of fluorouracil and leucovorin therapy versus fluorouracil, leucovorin, and cisplatin therapy in patients with advanced colorectal cancer. Cancer 73: 1562–1568
Schnall SF and MacDonald JS (1996) Chemotherapy of adenocarcinoma of the pancreas. Semin Oncol 23: 220–228
Spitz FR, Abbruzzes JL, Lee JE, Pisters PWT, Lowy AM, Fenoglio CJ, Cleary KR, Janjan NA, Goswitz MS, Rich TA and Evans DB (1997) Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol 15: 928–937
Tepper JE, Nardi GL and Suit HD (1976) Carcinoma of the pancreas: review of the MGH experience from 1963–1973: analysis of surgical failure and implications for radiation therapy. Cancer 37: 1519–1524
Vokes EE, Weichselbaum RR and Mick R (1992) Favourable long-term survival following induction chemotherapy with cisplatin, fluorouracil, and leucovorin and concomitant chemoradiotherapy for locally advanced head and neck cancer. J Natl Cancer Inst 84: 877–882
Wagener D, Rougier P, Wils J, Duez N and Selleslags J for the EORTC Gastrointestinal Tract Cooperative Group: (1992) Combined radiochemotherapy for locally advanced pancreatic cancer. Proc Am Soc Clin Oncol 11: 166 (abstract)
Warshaw AL and Fernandez-Del Castillo CF (1992) Pancreatic carcinoma. N Engl J Med 326: 455–465
Weinerman BH and McCormick RE (1994) A phase II survival comparison of patients with adenocarcinoma of the pancreas treated with 5-fluorouracil and calcium leucovorin versus a matched tumor registry control population. Am J Clin Oncol 17: 467–469
Willett CG, Lewandrowski K, Warshaw AL, Efird J and Compton CC (1993) Resection margins in carcinoma of the head of the pancreas. Implications for radiation therapy. Ann Surg 217: 144–148
Yeo CJ, Cameron JL, Lillemore KD, Sitzmann JV, Hruban RH, Goodman SN, Dooley WC, Coleman J and Pitt HA (1995) Pancreaticoduodenectomy for cancer of the head of the pancreas: 201 patients. Ann Surg 221: 721–733
Yeung RS, Weese JL, Hoffman JP, Solin LJ, Paul AR, Engstrom PF, Litwin S, Kowalyshyn MJ and Eisenberg BL (1993) Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma: a phase II study. Cancer 72: 2124–2133
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Kornek, G., Schratter-Sehn, A., Marczell, A. et al. Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin. Br J Cancer 82, 98–103 (2000). https://doi.org/10.1054/bjoc.1999.0884
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.1999.0884
Keywords
This article is cited by
-
The investigation of 125I seed implantation as a salvage modality for unresectable pancreatic carcinoma
Journal of Experimental & Clinical Cancer Research (2013)
-
The technical feasibility of an image-guided intensity-modulated radiotherapy (IG-IMRT) to perform a hypofractionated schedule in terms of toxicity and local control for patients with locally advanced or recurrent pancreatic cancer
Radiation Oncology (2012)
-
Regional hyperthermia combined with chemoradiotherapy in primary or recurrent locally advanced pancreatic cancer
Strahlentherapie und Onkologie (2011)
-
The role of radiotherapy in locally advanced pancreatic carcinoma
Nature Reviews Gastroenterology & Hepatology (2010)
-
Combination therapy of S-1 and CDDP for patients with colorectal cancer
Journal of Cancer Research and Clinical Oncology (2007)