Abstract
A total of 20 patients with advanced pancreatic adenocarcinoma were enrolled in a phase II trial testing the activity of 5-fluorouracil given at 370 mg/m2 as a rapid i. v. bolus for 5 consecutive days, preceded by a rapid i. v. bolus of 200 mg/m2 5-methyltetrahydrofolic acid. The treatment was repeated every 4 weeks. The median age of the patients was 68 years and their median Eastern Cooperative Oncology Group (ECOG) performance status was 1. There were 7 patients with locally advanced disease and 13 with distant metastases (median, 2 sites). A median of 3 monthly cycles of treatment (range, 1–7) were given, with a corresponding dose intensity of 396 mg/m2 per week (86% of that planned). No complete response, 1 partial response, and 8 cases of disease stabilization were obtained. In general the regimen was well tolerated, with only 2 patients suffering from grade 3 stomatitis or diarrhea; the most common toxicity was nausea, which was experienced by almost 50% of the patients. The combination of 5-methyltetrahydrofolate plus 5-fluorouracil appears as little effective in this disease as 5-fluorouracil plus 5-formyltetrahydrofolate (leucovorin). It is suggested that bolus 5-fluorouracil is so inactive as an “effector agent” against pancreatic cancer that its biochemical modulation with exogenous high-dose reduced folates cannot improve the therapeutic outcome produced by the fluoropyrimidine in these patients.
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Abbreviations
- FUra:
-
5-fluorouracil
- LV:
-
5-formyltetrahydrofolic acid
- ME-THF:
-
5-methyltetrahydrofolic acid
References
Crown J, Casper ES, Botet J, Murray P, Kelsen DP (1991) Lack of efficacy of high-dose leucovorin and fluorouracil in patients with advanced pancreatic adenocarcinoma. J Clin Oncol 9: 1682–1686
De Caorio JA, Mayer RJ, Gonin R, et al (1991) Fluorouracil and high-dose leucovorin in previously untreated patients with advanced adenocarcinoma of the pancreas: result of a phase II trial. J Clin Oncol 9: 2128–2133
Dobelbower RR Jr, Konsk AA, Merrick HW III, Bronn DG, et al (1991) Intraoperative electron beam radiation therapy (IOEBRT) for carcinoma of the exocrine pancreas. Int J Radiat Oncol Biol Phys 20: 113–119
Friedman MA, Cassidy MJ, Hannigan JF, et al (1981) A phase III study of adriamycin +5-FU vs BCNU+adriamycin+ftorafur for patients with advanced pancreatic cancer. Proc Am Assoc Cancer Res Am Soc Clin Oncol 22: 156
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
Gudjonsson B (1987) Cancer of the pancreas. Cancer 60: 2284–2303
Houghton JA, Williams LG, Graf S de, et al (1989) Comparison of the conversion of 5-formyl-tetrahydrofolate and 5-methyl-tetrahydrofolate to 5,10-methylene-tetrahydrofolates and tetrahydrofolates in human colon tumor. Cancer Commun 1: 167–174
Kalser MH, Ellenberg SS (1985) Pancreatic cancer: adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120: 899–903
Kelsen D, Hudis C, Niedzwiecki D, et al (1991) A phase III comparison trial of streptozotocin, mitomycin, and 5-fluorouracil with cisplatin, cytosine arabinoside, and caffeine in patients with advanced pancreatic carcinoma. Cancer 68: 965–969
Mallinson CN, Rake MO, Cocking JB, et al. (1980) Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomized, multicentre trial. BMJ 281: 1589–1591
Marsh JC, Bertino JR, Katz KH, et al (1991) The influence of drug interval on the effect of methotrexate and fluorouracil in the treatment of advanced colorectal cancer. J Clin Oncol 9: 371–380
Moertel CG, Frytak S, Hahn RG, et al (1981) Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high-dose (6000 rad) radiation alone, moderate-dose radiation (4000 rad + 5-fluorouracil), and high-dose radiation + 5-fluorouracil. Cancer 48: 1705–1710
Moran RG (1989) Leucovorin enhancement of the effects of the fluoropyrimidines on thymidylate synthase. Cancer 63: 1008–1012
Piedbois P, Buyese M, Rustum D, et al (1992) Advanced Colorectal Cancer Meta-Analysis Project. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. J Clin Oncol 10: 896–903
Shane B (1989) Folylglutamate synthesis and role in the regulation of one carbon metabolism. Vitam Horm 45: 263–335
Simon R (1989) Optimal two-stage designs for phase II clinical trials. Controlled Clin Trials 10: 1–10
Sobrero A, Rosso R, Bolli E, Tixi L, Falcone A, Conte PF, et al (1992) Phase II study of 5-FU plus 6-S-leucovorin (6S-LV) in advanced colorectal cancer. Proc Am Soc Clin Oncol 11: 1078
Swain SM, Lippman ME, Egan EF, Drake JC, Steinberg SM, Allegra JC (1989) Fluorouracil and high-dose leucovorin in previously treated patients with metastatic breast cancer. J Clin Oncol 7: 890–899
Vokes EE, Schilsky RL, Weichselbaum RR, et al (1989) Cisplatin, 5-fluorouracil, and high-dose oral leucovorin for advanced head and neck cancer. Cancer 63: 1048
Warshaw AL, Fernandez-Del Castillo C (1992) Pancreatic carcinoma. N Engl J Med 326: 455–465
Wils JA, Klein HO, Wagener DJ, et al (1991) Sequential high-dose methotrexate and fluorouracil combined with doxorubicin. A step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group. J Clin Oncol 9: 827–831
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Supported by CNR grant 92.01289.PF70, 92.02271.PF39 and AIRC 1994. A Guglielmi is a fellow of the Associazione Italiana Ricerca Cancro
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Bolli, E., Saccomanno, S., Mondini, G. et al. 5-Fluorouracil plus 5-methyltetrahydrofolate in advanced pancreatic cancer. Cancer Chemother. Pharmacol. 35, 339–342 (1995). https://doi.org/10.1007/BF00689455
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DOI: https://doi.org/10.1007/BF00689455