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British Journal of Cancer logoLink to British Journal of Cancer
. 1996 May;73(10):1260–1264. doi: 10.1038/bjc.1996.241

A phase II study of continuous-infusion 5-fluorouracil with cisplatin and epirubicin in inoperable pancreatic cancer.

T R Evans 1, F J Lofts 1, J L Mansi 1, J P Glees 1, A G Dalgleish 1, M J Knight 1
PMCID: PMC2074505  PMID: 8630289

Abstract

Carcinomas of the exocrine pancreas respond poorly to most chemotherapy regimens. Recently continuous infusional 5-fluorouracil (200 mg m-(2)day-1) with 3 weekly cisplatin (60 mg m-2) and epirubicin (50 mg m-2) (the ECF regimen) has proven to be an active regimen in gastric and breast cancer and consequently worthy of further study in pancreatic cancer. Thirty-five patients were treated with the ECF regimen as above, of whom 29 were evaluable for response and 32 were evaluable for toxicity. The mean age was 59 years (range 37-75). Sixteen patients had locally advanced disease at presentation and 19 had metastases. Objective tumour responses were documented in five (17.3%) patients who achieved a partial response; in 18 (62%) patients there were no change and six (20.7%) patients progressed on therapy. Patients with either stable disease or partial response had a significantly improved overall survival (median = 253 days) compared with patients who progressed (median = 170 days; P = 0.01). Grade 3/4 (WHO) toxicity (all cycles) included alopecia in 18 (56%) patients, nausea/vomiting in eight (25%) stomatitis in three (9%) and diarrhoea in seven (22%) patients, with rhinorrhoea and excessive lacrimation in one patient each. Neutropenic sepsis occurred in 13 cycles in ten patients, and there was one toxic death due to sepsis. There were eight other episodes of non-neutropenic sepsis requiring hospital admission. Fourteen patients (40%) experienced complications with their Hickman lines, including thrombotic episodes (six patients) or their line falling out (five patients). ECF can prolong survival in patients with locally advanced or metastatic pancreatic cancer who demonstrate a response or stabilisation of their disease. However, this is associated with considerable toxicity.

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Selected References

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  1. Bern M. M., Lokich J. J., Wallach S. R., Bothe A., Jr, Benotti P. N., Arkin C. F., Greco F. A., Huberman M., Moore C. Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial. Ann Intern Med. 1990 Mar 15;112(6):423–428. doi: 10.7326/0003-4819-76-3-112-6-423. [DOI] [PubMed] [Google Scholar]
  2. Buroker T., Kim P. N., Groppe C., McCracken J., O'Bryan R., Panettiere F., Costanzi J., Bottomley R., King G. W., Bonnet J. 5 FU infusion with mitomycin-C vs. 5 FU infusion with methyl-CCNU in the treatment of advanced upper gastrointestinal cancer: a Southwest Oncology Group Study. Cancer. 1979 Oct;44(4):1215–1221. doi: 10.1002/1097-0142(197910)44:4<1215::aid-cncr2820440408>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  3. Calvert A. H., Newell D. R., Gumbrell L. A., O'Reilly S., Burnell M., Boxall F. E., Siddik Z. H., Judson I. R., Gore M. E., Wiltshaw E. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989 Nov;7(11):1748–1756. doi: 10.1200/JCO.1989.7.11.1748. [DOI] [PubMed] [Google Scholar]
  4. Carter S. K., Comis R. L. The integration of chemotherapy into a combined modality approach for cancer treatment. VI. Pancreatic adenocarcinoma. Cancer Treat Rev. 1975 Sep;2(3):193–214. doi: 10.1016/s0305-7372(75)80003-x. [DOI] [PubMed] [Google Scholar]
  5. Findlay M., Cunningham D., Norman A., Mansi J., Nicolson M., Hickish T., Nicolson V., Nash A., Sacks N., Ford H. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609–616. doi: 10.1093/oxfordjournals.annonc.a058932. [DOI] [PubMed] [Google Scholar]
  6. Jones A. L., Smith I. E., O'Brien M. E., Talbot D., Walsh G., Ramage F., Robertshaw H., Ashley S. Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen. J Clin Oncol. 1994 Jun;12(6):1259–1265. doi: 10.1200/JCO.1994.12.6.1259. [DOI] [PubMed] [Google Scholar]
  7. Kovach J. S., Moertel C. G., Schutt A. J., Hahn R. G., Reitemeier R. J. Proceedings: A controlled study of combined 1,3-bis-(2-chloroethyl)-1-nitrosourea and 5-fluorouracil therapy for advanced gastric and pancreatic cancer. Cancer. 1974 Feb;33(2):563–567. doi: 10.1002/1097-0142(197402)33:2<563::aid-cncr2820330235>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  8. Lokich J. J., Ahlgren J. D., Gullo J. J., Philips J. A., Fryer J. G. A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study. J Clin Oncol. 1989 Apr;7(4):425–432. doi: 10.1200/JCO.1989.7.4.425. [DOI] [PubMed] [Google Scholar]
  9. Mallinson C. N., Rake M. O., Cocking J. B., Fox C. A., Cwynarski M. T., Diffey B. L., Jackson G. A., Hanley J., Wass V. J. Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomised, multicentre trial. Br Med J. 1980 Dec 13;281(6255):1589–1591. doi: 10.1136/bmj.281.6255.1589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  11. Moertel C. G. Chemotherapy of gastrointestinal cancer. Clin Gastroenterol. 1976 Sep;5(3):777–793. [PubMed] [Google Scholar]
  12. Oster M. W., Gray R., Panasci L., Perry M. C. Chemotherapy for advanced pancreatic cancer. A comparison of 5-fluorouracil, adriamycin, and mitomycin (FAM) with 5-fluorouracil, streptozotocin, and mitomycin (FSM). Cancer. 1986 Jan 1;57(1):29–33. doi: 10.1002/1097-0142(19860101)57:1<29::aid-cncr2820570108>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  13. Palmer K. R., Kerr M., Knowles G., Cull A., Carter D. C., Leonard R. C. Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Br J Surg. 1994 Jun;81(6):882–885. doi: 10.1002/bjs.1800810629. [DOI] [PubMed] [Google Scholar]
  14. Rothman H., Cantrell J. E., Jr, Lokich J., Difino S., Harvey J., Ahlgren J., Fryer J. Continuous infusion 5-fluorouracil plus weekly cisplatin for pancreatic carcinoma. A Mid-Atlantic Oncology Program study. Cancer. 1991 Jul 15;68(2):264–268. doi: 10.1002/1097-0142(19910715)68:2<264::aid-cncr2820680208>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  15. Rougier P., Zarba J. J., Ducreux M., Basile M., Pignon J. P., Mahjoubi M., Benahmed M., Droz J. P., Cvitkovic E., Armand J. P. Phase II study of cisplatin and 120-hour continuous infusion of 5-fluorouracil in patients with advanced pancreatic adenocarcinoma. Ann Oncol. 1993 Apr;4(4):333–336. doi: 10.1093/oxfordjournals.annonc.a058495. [DOI] [PubMed] [Google Scholar]
  16. Sack G. H., Jr, Levin J., Bell W. R. Trousseau's syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine (Baltimore) 1977 Jan;56(1):1–37. [PubMed] [Google Scholar]
  17. Scanlon K. J., Newman E. M., Lu Y., Priest D. G. Biochemical basis for cisplatin and 5-fluorouracil synergism in human ovarian carcinoma cells. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8923–8925. doi: 10.1073/pnas.83.23.8923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Stacey R. G., Filshie J., Skewes D. Percutaneous insertion of Hickman-type catheters. Br J Hosp Med. 1991 Dec;46(6):396–398. [PubMed] [Google Scholar]
  19. Williamson R. C. Pancreatic cancer: the greatest oncological challenge. Br Med J (Clin Res Ed) 1988 Feb 13;296(6620):445–446. doi: 10.1136/bmj.296.6620.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wils J. A., Kok T., Wagener D. J., Selleslags J., Duez N. Activity of cisplatin in adenocarcinoma of the pancreas. Eur J Cancer. 1993;29A(2):203–204. doi: 10.1016/0959-8049(93)90175-f. [DOI] [PubMed] [Google Scholar]
  21. Wils J., Bleiberg H., Blijham G., Dalesio O., Duez N., Lacave A., Splinter T. Phase II study of epirubicin in advanced adenocarcinoma of the pancreas. Eur J Cancer Clin Oncol. 1985 Feb;21(2):191–194. doi: 10.1016/0277-5379(85)90172-5. [DOI] [PubMed] [Google Scholar]

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