This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maisey, N. Articles by Hill, M. Search for Related Content PubMed PubMed Citation Articles by Maisey, N. Articles by Hill, M. Social Bookmarking                            What's this?

Multicenter Randomized Phase III Trial Comparing Protracted Venous Infusion (PVI) Fluorouracil (5-FU) With PVI 5-FU Plus Mitomycin in Inoperable Pancreatic Cancer

From the Royal Marsden Hospital, Surrey; Cookridge Hospital, Leeds; Royal Bournemouth Hospital, Bournemouth; Salisbury General Hospital, Salisbury; and Maidstone General Hospital, Maidstone, United Kingdom.

Address reprint requests to D. Cunningham, MD, Department of Medicine, Royal Marsden Hospital, Downs Rd, Sutton, Surrey, SM2 5PT United Kingdom; email: dcunn{at}icr.ac.uk

PURPOSE: To compare protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin (MMC) in patients with advanced pancreatic cancer in a multicenter, prospectively randomized study.

PATIENTS AND METHODS: Two hundred eight patients were randomized to PVI 5-FU (300 mg/m²/d for a maximum of 24 weeks) or PVI 5-FU plus MMC (7 mg/m² every 6 weeks for four courses). The major end points were tumor response, survival, toxicity, and quality of life (QOL).

RESULTS: The two treatment groups were balanced for baseline demographic factors, and 62% had metastatic disease. The overall response rate was 8.4% (95% confidence interval [CI]) 3.2% to 13.7% for patients treated with PVI 5-FU alone compared with 17.6%; 95% CI 10.3% to 25.1% for PVI 5-FU plus MMC (P = .04). Median failure-free survival was 2.8 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC (P = .14). Median survival was 5.1 months for PVI 5-FU and 6.5 months for PVI 5-FU plus MMC (P = .34). Toxicities in both arms were mild. There was an increased incidence of neutropenia in the 5-FU plus MMC arm (P < .01), although no differences in infection were seen. No patients developed hemolytic uremic syndrome. Global QOL improved significantly after 24 weeks of treatment compared with baseline for patients receiving 5-FU plus MMC, although there was no statistically significant difference in QOL between arms.

CONCLUSION: PVI 5-FU plus MMC resulted in a superior response rate in comparison with PVI 5-FU alone in advanced pancreatic cancer, but this did not translate into a survival advantage. These results emphasize the importance of chemotherapy in this setting and the continuing value of the fluoropyrimidines in pancreatic cancer.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. Sultana, C. T. Smith, D. Cunningham, N. Starling, J. P. Neoptolemos, and P. Ghaneh Meta-Analyses of Chemotherapy for Locally Advanced and Metastatic Pancreatic Cancer J. Clin. Oncol., June 20, 2007; 25(18): 2607 - 2615. [Abstract] [Full Text] [PDF]

				J Taieb, T Lecomte, T Aparicio, A Asnacios, T Mansourbakht, P Artru, D Fallik, J. Spano, B Landi, G Lledo, et al. FOLFIRI.3, a new regimen combining 5-fluorouracil, folinic acid and irinotecan, for advanced pancreatic cancer: results of an Association des Gastro-Enterologues Oncologues (Gastroenterologist Oncologist Association) multicenter phase II study Ann. Onc., March 1, 2007; 18(3): 498 - 503. [Abstract] [Full Text] [PDF]

				J. G. Trevino, J. M. Summy, D. P. Lesslie, N. U. Parikh, D. S. Hong, F. Y. Lee, N. J. Donato, J. L. Abbruzzese, C. H. Baker, and G. E. Gallick Inhibition of Src Expression and Activity Inhibits Tumor Progression and Metastasis of Human Pancreatic Adenocarcinoma Cells in an Orthotopic Nude Mouse Model Am. J. Pathol., March 1, 2006; 168(3): 962 - 972. [Abstract] [Full Text] [PDF]

				J. G. Trevino, J. M. Summy, M. J. Gray, M. B. Nilsson, D. P. Lesslie, C. H. Baker, and G. E. Gallick Expression and Activity of Src Regulate Interleukin-8 Expression in Pancreatic Adenocarcinoma Cells: Implications for Angiogenesis Cancer Res., August 15, 2005; 65(16): 7214 - 7222. [Abstract] [Full Text] [PDF]

				Y. J. Chua and D. Cunningham Adjuvant Treatment for Resectable Pancreatic Cancer J. Clin. Oncol., July 10, 2005; 23(20): 4532 - 4537. [Abstract] [Full Text] [PDF]

				Pancreatic Section Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas Gut, June 1, 2005; 54(suppl_5): v1 - v16. [Full Text] [PDF]

				T. Conroy, B. Paillot, E. Francois, R. Bugat, J.-H. Jacob, U. Stein, S. Nasca, J.-P. Metges, O. Rixe, P. Michel, et al. Irinotecan Plus Oxaliplatin and Leucovorin-Modulated Fluorouracil in Advanced Pancreatic Cancer--A Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer Study J. Clin. Oncol., February 20, 2005; 23(6): 1228 - 1236. [Abstract] [Full Text] [PDF]

				M. Ducreux, E. Mitry, M. Ould-Kaci, V. Boige, J. F. Seitz, R. Bugat, J. L. Breau, O. Bouche, P. L. Etienne, J. M. Tigaud, et al. Response to the letter "Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU and infusional 5-FU alone in advanced pancreatic carcinoma patients", by C. Allior (Ann. Oncol 2004; 15: 1576-1577) Ann. Onc., October 1, 2004; 15(10): 1577 - 1578. [Full Text] [PDF]

				M. Ducreux, E. Mitry, M. Ould-Kaci, V. Boige, J. F. Seitz, R. Bugat, J. L. Breau, O. Bouche, P. L. Etienne, J. M. Tigaud, et al. Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients Ann. Onc., March 1, 2004; 15(3): 467 - 473. [Abstract] [Full Text] [PDF]

				B.F. El-Rayes, M.M. Zalupski, A.F. Shields, U. Vaishampayan, L.K. Heilbrun, V. Jain, V. Adsay, J. Day, and P.A. Philip Phase II Study of Gemcitabine, Cisplatin, and Infusional Fluorouracil in Advanced Pancreatic Cancer J. Clin. Oncol., August 1, 2003; 21(15): 2920 - 2925. [Abstract] [Full Text] [PDF]

				Management of pancreatic cancer DTB, May 1, 2003; 41(5): 36 - 40. [Abstract] [Full Text] [PDF]

				J. P. Neoptolemos, D. Cunningham, H. Friess, C. Bassi, D. D. Stocken, D. M. Tait, J. A. Dunn, C. Dervenis, F. Lacaine, H. Hickey, et al. Adjuvant therapy in pancreatic cancer: historical and current perspectives Ann. Onc., May 1, 2003; 14(5): 675 - 692. [Abstract] [Full Text] [PDF]

				N. C. Tebbutt, A. Norman, D. Cunningham, T. Iveson, M. Seymour, T. Hickish, P. Harper, N. Maisey, K. Mochlinski, Y. Prior, et al. A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer Ann. Onc., October 1, 2002; 13(10): 1568 - 1575. [Abstract] [Full Text] [PDF]