Advertisement
Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO My JCO Subscriptions Customer Service Site Map

Journal of Clinical Oncology, Vol 22, No 18 (September 15), 2004: pp. 3766-3775
© 2004 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2004.03.104
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Erratum (v23,p1337)
Right arrow Erratum (v23,p1337)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Save to my personal folders
Right arrow Download to citation manager
Right arrowRights & Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Modulation of Fluorouracil by Leucovorin in Patients With Advanced Colorectal Cancer: An Updated Meta-Analysis

The Meta-Analysis Group in Cancer

From the Meta-Analysis Group in Cancer

Address reprint requests to Pascal Piedbois, MD, PhD, Department of Medical Oncology, Assistance Publique, Hopitaux de Paris, Henri Mondor Hospital, 94000 Creteil, France; e-mail: pascal.piedbois{at}hmn.ap-hop-paris.fr

PURPOSE: The modulation of fluorouracil (FU) by folinic acid (leucovorin [LV]) has been shown to be effective in terms of tumor response rate in patients with advanced colorectal cancer, but a meta-analysis of nine trials previously published by our group failed to demonstrate a statistically significant survival difference between FU and FU-LV. We present an update of the meta-analysis, with a longer follow-up and the inclusion of 10 newer trials.

PATIENTS AND METHODS: Analyses are based on individual data from 3,300 patients randomized in 19 trials on an intent-to-treat basis. Two trials had multiple comparisons, leading to a total of 21 pair-wise comparisons. FU doses were similar in both arms in 10 pair-wise comparisons, 15% to 33% higher in the FU-alone arm in six comparisons, and more than 66% higher in five comparisons.

RESULTS: Overall analysis showed a two-fold increase in tumor response rates (11% for FU-LV v 21% for FU alone; odds ratio, 0.53; 95% CI, 0.44 to 0.63; P < .0001) and a small but statistically significant overall survival benefit for FU-LV over FU alone (median survival, 11.7 v 10.5 months, respectively; hazards ratio, 0.90; 95% CI, 0.87 to 0.94; P = .004), which were primarily seen in the first year. We observed a significant interaction between treatment benefit and dose of FU, with tumor response and overall survival advantages of FU-LV over FU-alone being restricted to trials in which a similar dose of FU was prescribed in both arms.

CONCLUSION: This updated analysis demonstrates, on a large data set, that FU-LV improves both response rate and overall survival compared with FU alone and that this benefit is consistent across various prognostic factors.

{dagger}Deceased.

Supported by a grant from the French "Programme Hospitalier de Recherche Clinique" and by the European Association for Research in Oncology.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.


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


This article has been cited by other articles:


Home page
 Ann OncolHome page
K.-L. G. Spindler, R. F. Andersen, L. H. Jensen, J. Ploen, and A. Jakobsen
EGF61A>G polymorphism as predictive marker of clinical outcome to first-line capecitabine and oxaliplatin in metastatic colorectal cancer
Ann. Onc., October 22, 2009; (2009) mdp336v1.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
W. Koizumi, N. Boku, K. Yamaguchi, Y. Miyata, A. Sawaki, T. Kato, Y. Toh, I. Hyodo, T. Nishina, T. Furuhata, et al.
Phase II study of S-1 plus leucovorin in patients with metastatic colorectal cancer
Ann. Onc., October 14, 2009; (2009) mdp371v1.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
S. Afzal, S. A. Jensen, B. Vainer, U. Vogel, J. P. Matsen, J. B. Sorensen, P. K. Andersen, and H. E. Poulsen
MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer
Ann. Onc., October 1, 2009; 20(10): 1660 - 1666.
[Abstract] [Full Text] [PDF]

Home page
 Anticancer ResHome page
T. PALOMARES, M. CARAMES, I. GARCIA-ALONSO, and A. ALONSO-VARONA
Glutathione Modulation Reverses the Growth-promoting Effect of Growth Factors, Improving the 5-Fluorouracil Antitumour Response in WiDr Colon Cancer Cells
Anticancer Res, October 1, 2009; 29(10): 3957 - 3965.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
M. Ychou, W. Hohenberger, S. Thezenas, M. Navarro, J. Maurel, C. Bokemeyer, E. Shacham-Shmueli, F. Rivera, C. Kwok-Keung Choi, and A. Santoro
A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer
Ann. Onc., June 30, 2009; (2009) mdp236v1.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D. G. Power and N. E. Kemeny
The role of floxuridine in metastatic liver disease
Mol. Cancer Ther., May 1, 2009; 8(5): 1015 - 1025.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
C.-H. Kohne and H.-J. Lenz
Chemotherapy with Targeted Agents for the Treatment of Metastatic Colorectal Cancer
Oncologist, May 1, 2009; 14(5): 478 - 488.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
D. Cunningham, B. Sirohi, A. Pluzanska, B. Utracka-Hutka, J. Zaluski, R. Glynne-Jones, P. Koralewski, J. Bridgewater, P. Mainwaring, H. Wasan, et al.
Two different first-line 5-fluorouracil regimens with or without oxaliplatin in patients with metastatic colorectal cancer
Ann. Onc., February 1, 2009; 20(2): 244 - 250.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
H.-T. Arkenau, D. Arnold, J. Cassidy, E. Diaz-Rubio, J.-Y. Douillard, H. Hochster, A. Martoni, A. Grothey, A. Hinke, W. Schmiegel, et al.
Efficacy of Oxaliplatin Plus Capecitabine or Infusional Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer: A Pooled Analysis of Randomized Trials
J. Clin. Oncol., December 20, 2008; 26(36): 5910 - 5917.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
C. M. Sturgeon, M. J. Duffy, U.-H. Stenman, H. Lilja, N. Brunner, D. W. Chan, R. Babaian, R. C. Bast Jr., B. Dowell, F. J. Esteva, et al.
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers
Clin. Chem., December 1, 2008; 54(12): e11 - e79.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Schlemmer, M. Kuehl, A. Schalhorn, J. Rauch, K.-W. Jauch, and M. Hentrich
Tissue Levels of Reduced Folates in Patients with Colorectal Carcinoma After Infusion of Folinic Acid at Various Dose Levels
Clin. Cancer Res., December 1, 2008; 14(23): 7930 - 7934.
[Abstract] [Full Text] [PDF]

Home page
 Stat Methods Med ResHome page
A. Alonso and G. Molenberghs
Evaluating time to cancer recurrence as a surrogate marker for survival from an information theory perspective
Statistical Methods in Medical Research, October 1, 2008; 17(5): 497 - 504.
[Abstract] [PDF]

Home page
 Stat Methods Med ResHome page
M. D Hughes
Practical issues arising in an exploratory analysis evaluating progression-free survival as a surrogate endpoint for overall survival in advanced colorectal cancer
Statistical Methods in Medical Research, October 1, 2008; 17(5): 487 - 495.
[Abstract] [PDF]

Home page
 Stat Methods Med ResHome page
S. G Baker
Two simple approaches for validating a binary surrogate endpoint using data from multiple trials
Statistical Methods in Medical Research, October 1, 2008; 17(5): 505 - 514.
[Abstract] [PDF]

Home page
 Stat Methods Med ResHome page
T. Burzykowski
Surrogate endpoints: wishful thinking or reality?
Statistical Methods in Medical Research, October 1, 2008; 17(5): 463 - 466.
[PDF]

Home page
 JCOHome page
B. M. Wolpin, E. K. Wei, K. Ng, J. A. Meyerhardt, J. A. Chan, J. Selhub, E. L. Giovannucci, and C. S. Fuchs
Prediagnostic Plasma Folate and the Risk of Death in Patients With Colorectal Cancer
J. Clin. Oncol., July 1, 2008; 26(19): 3222 - 3228.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. Schwab, U. M. Zanger, C. Marx, E. Schaeffeler, K. Klein, J. Dippon, R. Kerb, J. Blievernicht, J. Fischer, U. Hofmann, et al.
Role of Genetic and Nongenetic Factors for Fluorouracil Treatment-Related Severe Toxicity: A Prospective Clinical Trial by the German 5-FU Toxicity Study Group
J. Clin. Oncol., May 1, 2008; 26(13): 2131 - 2138.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
C.-H. Kohne, J. De Greve, J. T. Hartmann, I. Lang, P. Vergauwe, K. Becker, D. Braumann, E. Joosens, L. Muller, J. Janssens, et al.
Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015
Ann. Onc., May 1, 2008; 19(5): 920 - 926.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. Buyse, T. Burzykowski, K. Carroll, S. Michiels, D. J. Sargent, L. L. Miller, G. L. Elfring, J.-P. Pignon, and P. Piedbois
Progression-Free Survival Is a Surrogate for Survival in Advanced Colorectal Cancer
J. Clin. Oncol., November 20, 2007; 25(33): 5218 - 5224.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. Porschen, H.-T. Arkenau, S. Kubicka, R. Greil, T. Seufferlein, W. Freier, A. Kretzschmar, U. Graeven, A. Grothey, A. Hinke, et al.
Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Leucovorin Plus Oxaliplatin in Metastatic Colorectal Cancer: A Final Report of the AIO Colorectal Study Group
J. Clin. Oncol., September 20, 2007; 25(27): 4217 - 4223.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. P. Lutz, H. Wilke, D.J. T. Wagener, U. Vanhoefer, K. Jeziorski, S. Hegewisch-Becker, L. Balleisen, E. Joossens, R. L. Jansen, M. Debois, et al.
Weekly Infusional High-Dose Fluorouracil (HD-FU), HD-FU Plus Folinic Acid (HD-FU/FA), or HD-FU/FA Plus Biweekly Cisplatin in Advanced Gastric Cancer: Randomized Phase II Trial 40953 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group and the Arbeitsgemeinschaft Internistische Onkologie
J. Clin. Oncol., June 20, 2007; 25(18): 2580 - 2585.
[Abstract] [Full Text] [PDF]

Home page
 J Oncol Pharm PractHome page
J. Cadrobbi, J.-D. Hecq, D. Vanbeckbergen, J. Jamart, and L. Galanti
Long-term stability of sodium folinate in dextrose 5% polyolefin bags at 4{degrees}C
Journal of Oncology Pharmacy Practice, June 1, 2007; 13(2): 99 - 103.
[Abstract] [PDF]

Home page
 CA Cancer J ClinHome page
B. M. Wolpin, J. A. Meyerhardt, H. J. Mamon, and R. J. Mayer
Adjuvant Treatment of Colorectal Cancer
CA Cancer J Clin, May 1, 2007; 57(3): 168 - 185.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
G. Portier, D. Elias, O. Bouche, P. Rougier, J.-F. Bosset, J. Saric, J. Belghiti, P. Piedbois, R. Guimbaud, B. Nordlinger, et al.
Multicenter Randomized Trial of Adjuvant Fluorouracil and Folinic Acid Compared With Surgery Alone After Resection of Colorectal Liver Metastases: FFCD ACHBTH AURC 9002 Trial
J. Clin. Oncol., November 1, 2006; 24(31): 4976 - 4982.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
X. Wu, J. Gu, T.-T. Wu, S. G. Swisher, Z. Liao, A. M. Correa, J. Liu, C. J. Etzel, C. I. Amos, M. Huang, et al.
Genetic Variations in Radiation and Chemotherapy Drug Action Pathways Predict Clinical Outcomes in Esophageal Cancer
J. Clin. Oncol., August 10, 2006; 24(23): 3789 - 3798.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. Ichikawa, T. Takahashi, K. Suto, Y. Sasaki, and R. Hirayama
Orotate Phosphoribosyltransferase Gene Polymorphism Predicts Toxicity in Patients Treated with Bolus 5-Fluorouracil Regimen.
Clin. Cancer Res., July 1, 2006; 12(13): 3928 - 3934.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Ciomei, V. Croci, A. Ciavolella, D. Ballinari, and E. Pesenti
Antitumor efficacy of edotecarin as a single agent and in combination with chemotherapy agents in a xenograft model.
Clin. Cancer Res., May 1, 2006; 12(9): 2856 - 2861.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
C. Leonetti, M. Scarsella, G. Zupi, W. Zoli, D. Amadori, L. Medri, F. Fabbri, M. Rosetti, P. Ulivi, L. Cecconetto, et al.
Efficacy of a nitric oxide-releasing nonsteroidal anti-inflammatory drug and cytotoxic drugs in human colon cancer cell lines in vitro and xenografts.
Mol. Cancer Ther., April 1, 2006; 5(4): 919 - 926.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
C. H. Smorenburg, G. J. Peters, C. J. van Groeningen, P. Noordhuis, K. Smid, A. M. G. H. van Riel, W. Dercksen, H. M. Pinedo, and G. Giaccone
Phase II study of tailored chemotherapy for advanced colorectal cancer with either 5-fluouracil and leucovorin or oxaliplatin and irinotecan based on the expression of thymidylate synthase and dihydropyrimidine dehydrogenase
Ann. Onc., January 1, 2006; 17(1): 35 - 42.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
F. F. Kabbinavar, J. Hambleton, R. D. Mass, H. I. Hurwitz, E. Bergsland, and S. Sarkar
Combined Analysis of Efficacy: The Addition of Bevacizumab to Fluorouracil/Leucovorin Improves Survival for Patients With Metastatic Colorectal Cancer
J. Clin. Oncol., June 1, 2005; 23(16): 3706 - 3712.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
P. Comella, B. Massidda, G. Filippelli, S. Palmeri, D. Natale, A. Farris, F. De Vita, F. Buzzi, S. Tafuto, L. Maiorino, et al.
Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial
Ann. Onc., June 1, 2005; 16(6): 878 - 886.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
H. I. Hurwitz, L. Fehrenbacher, J. D. Hainsworth, W. Heim, J. Berlin, E. Holmgren, J. Hambleton, W. F. Novotny, and F. Kabbinavar
Bevacizumab in Combination With Fluorouracil and Leucovorin: An Active Regimen for First-Line Metastatic Colorectal Cancer
J. Clin. Oncol., May 20, 2005; 23(15): 3502 - 3508.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
H. Hurwitz
New Combinations in Metastatic Colorectal Cancer: What Are Our Expectations?
Oncologist, May 1, 2005; 10(5): 320 - 322.
[Full Text] [PDF]

Home page
 The OncologistHome page
A. Venook
Critical Evaluation of Current Treatments in Metastatic Colorectal Cancer
Oncologist, April 1, 2005; 10(4): 250 - 261.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
J. A. Meyerhardt and R. J. Mayer
Systemic Therapy for Colorectal Cancer
N. Engl. J. Med., February 3, 2005; 352(5): 476 - 487.
[Full Text] [PDF]


About
JCO		 Editorial
Roster		 Advertising
Information		 Librarians &
Institutions		 Rights &
Permissions		 PDA Services

Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online