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. 1999 Jul;80(10):1595–1598. doi: 10.1038/sj.bjc.6690568

A combination of gemcitabine and 5-fluorouracil in advanced pancreatic cancer, a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)

S Cascinu 1, R R Silva 2, S Barni 3, R Labianca 4, L Frontini 5, E Piazza 6, G Pancera 7, P Giordani 1, L Giuliodori 2, M A Pessi 4, V Fusco 8, G Luporini 4, R Cellerino 9, G Catalano 1
PMCID: PMC2363090  PMID: 10408405

Abstract

In a randomized clinical trial, gemcitabine (GEM) was more effective than 5-fluorouracil (5-FU) in advanced pancreatic cancer patients. GEM and 5-FU have different mechanisms of action and their combination, from a theoretical point of view, could result in a higher activity. To test activity and feasibility of such a combination, a multi-institutional phase II study was initiated in November 1996 by the Italian Group for the study of Digestive Tract Cancer (GISCAD). Primary objectives of this study were to determine the activity in terms of response rate and clinical benefit, while the secondary objective was toxicity. According to the optimal two-stage phase II design, 54 patients were enrolled. Schedule was: GEM 1000 mg m−2 intravenous (i.v.), and 5-FU 600 mg m−2 bolus i.v. weekly for 3 weeks out of every 4. All the 54 patients were symptomatic (pain, weight loss, dyspepsia). A clinical benefit was obtained in 28 patients (51%) (95% confidence interval (CI) 38–64%). Two patients achieved a partial response and 34 a stable disease. Median survival for all the patients was 7 months. Side-effects were mild: no gastrointestinal or haematological grade 3–4 toxicity (WHO) were recorded. We observed only six episodes of grade 2 (WHO) leukopenia and seven episodes of thrombocytopenia. Although the non-randomized design of this study suggests caution in the interpretation of these data, in consideration of the low incidence of toxicity and the favourable results obtained in terms of clinical benefit, it may be worthwhile to test more active schedules of 5-FU (continuous infusion) in combination with gemcitabine. © 1999 Cancer Research Campaign

Keywords: pancreatic cancer, intensive chemotherapy, palliation

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Selected References

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  1. Ahlgren J. D. Chemotherapy for pancreatic carcinoma. Cancer. 1996 Aug 1;78(3 Suppl):654–663. doi: 10.1002/(SICI)1097-0142(19960801)78:3<654::AID-CNCR46>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
  2. Burris H. A., 3rd, Moore M. J., Andersen J., Green M. R., Rothenberg M. L., Modiano M. R., Cripps M. C., Portenoy R. K., Storniolo A. M., Tarassoff P. 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 Jun;15(6):2403–2413. doi: 10.1200/JCO.1997.15.6.2403. [DOI] [PubMed] [Google Scholar]
  3. Carmichael J., Fink U., Russell R. C., Spittle M. F., Harris A. L., Spiessi G., Blatter J. Phase II study of gemcitabine in patients with advanced pancreatic cancer. Br J Cancer. 1996 Jan;73(1):101–105. doi: 10.1038/bjc.1996.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Casper E. S., Green M. R., Kelsen D. P., Heelan R. T., Brown T. D., Flombaum C. D., Trochanowski B., Tarassoff P. G. Phase II trial of gemcitabine (2,2'-difluorodeoxycytidine) in patients with adenocarcinoma of the pancreas. Invest New Drugs. 1994;12(1):29–34. doi: 10.1007/BF00873232. [DOI] [PubMed] [Google Scholar]
  5. DeCaprio J. A., Mayer R. J., Gonin R., Arbuck S. G. Fluorouracil and high-dose leucovorin in previously untreated patients with advanced adenocarcinoma of the pancreas: results of a phase II trial. J Clin Oncol. 1991 Dec;9(12):2128–2133. doi: 10.1200/JCO.1991.9.12.2128. [DOI] [PubMed] [Google Scholar]
  6. Grindey G. B., Hertel L. W., Plunkett W. Cytotoxicity and antitumor activity of 2',2'-difluorodeoxycytidine (Gemcitabine). Cancer Invest. 1990;8(2):313–313. doi: 10.3109/07357909009017602. [DOI] [PubMed] [Google Scholar]
  7. Heinemann V., Xu Y. Z., Chubb S., Sen A., Hertel L. W., Grindey G. B., Plunkett W. Inhibition of ribonucleotide reduction in CCRF-CEM cells by 2',2'-difluorodeoxycytidine. Mol Pharmacol. 1990 Oct;38(4):567–572. [PubMed] [Google Scholar]
  8. Kelly D. M., Benjamin I. S. Pancreatic carcinoma. Ann Oncol. 1995 Jan;6(1):19–28. doi: 10.1093/oxfordjournals.annonc.a059031. [DOI] [PubMed] [Google Scholar]
  9. Lionetto R., Pugliese V., Bruzzi P., Rosso R. No standard treatment is available for advanced pancreatic cancer. Eur J Cancer. 1995 Jun;31A(6):882–887. doi: 10.1016/0959-8049(94)00445-5. [DOI] [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. Moore M. Activity of gemcitabine in patients with advanced pancreatic carcinoma. A review. Cancer. 1996 Aug 1;78(3 Suppl):633–638. doi: 10.1002/(SICI)1097-0142(19960801)78:3<633::AID-CNCR44>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  12. Parker S. L., Tong T., Bolden S., Wingo P. A. Cancer statistics, 1997. CA Cancer J Clin. 1997 Jan-Feb;47(1):5–27. doi: 10.3322/canjclin.47.1.5. [DOI] [PubMed] [Google Scholar]
  13. Popescu R. A., Cunningham D. Chemotherapy for advanced pancreatic cancer--some light at the end of the tunnel? Ann Oncol. 1997 May;8(5):415–416. doi: 10.1023/a:1008292224326. [DOI] [PubMed] [Google Scholar]
  14. Rothenberg M. L., Abbruzzese J. L., Moore M., Portenoy R. K., Robertson J. M., Wanebo H. J. A rationale for expanding the endpoints for clinical trials in advanced pancreatic carcinoma. Cancer. 1996 Aug 1;78(3 Suppl):627–632. doi: 10.1002/(SICI)1097-0142(19960801)78:3<627::AID-CNCR43>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
  15. Rothenberg M. L., Moore M. J., Cripps M. C., Andersen J. S., Portenoy R. K., Burris H. A., 3rd, Green M. R., Tarassoff P. G., Brown T. D., Casper E. S. A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol. 1996 Apr;7(4):347–353. doi: 10.1093/oxfordjournals.annonc.a010600. [DOI] [PubMed] [Google Scholar]
  16. Scher R. M., Kosierowski R., Lusch C., Alexander R., Fox S., Redei I., Green F., Raskay B., Amfoh K., Engstrom P. F. Phase II trial of topotecan in advanced or metastatic adenocarcinoma of the pancreas. Invest New Drugs. 1996;13(4):347–354. doi: 10.1007/BF00873143. [DOI] [PubMed] [Google Scholar]
  17. Schnall S. F., Macdonald J. S. Chemotherapy of adenocarcinoma of the pancreas. Semin Oncol. 1996 Apr;23(2):220–228. [PubMed] [Google Scholar]
  18. Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1–10. doi: 10.1016/0197-2456(89)90015-9. [DOI] [PubMed] [Google Scholar]
  19. Taylor I. Should further studies of chemotherapy be carried out in pancreatic cancer? Eur J Cancer. 1993;29A(8):1076–1078. doi: 10.1016/s0959-8049(05)80290-4. [DOI] [PubMed] [Google Scholar]
  20. Wagener D. J., Verdonk H. E., Dirix L. Y., Catimel G., Siegenthaler P., Buitenhuis M., Mathieu-Boué A., Verweij J. Phase II trial of CPT-11 in patients with advanced pancreatic cancer, an EORTC early clinical trials group study. Ann Oncol. 1995 Feb;6(2):129–132. doi: 10.1093/oxfordjournals.annonc.a059107. [DOI] [PubMed] [Google Scholar]
  21. Whitehead R. P., Jacobson J., Brown T. D., Taylor S. A., Weiss G. R., Macdonald J. S. Phase II trial of paclitaxel and granulocyte colony-stimulating factor in patients with pancreatic carcinoma: a Southwest Oncology Group study. J Clin Oncol. 1997 Jun;15(6):2414–2419. doi: 10.1200/JCO.1997.15.6.2414. [DOI] [PubMed] [Google Scholar]

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