Originally published as JCO Early Release 10.1200/JCO.2008.21.6663 on May 18 2009

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 Van Cutsem, E. Articles by Cunningham, D. Search for Related Content PubMed PubMed Citation Articles by Van Cutsem, E. Articles by Cunningham, D. Related Articles Related Article Social Bookmarking                            What's this?

Randomized Phase III Trial Comparing Biweekly Infusional Fluorouracil/Leucovorin Alone or With Irinotecan in the Adjuvant Treatment of Stage III Colon Cancer: PETACC-3

From the Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven; European Organisation for Research and Treatment of Cancer Headquarters, Statistics Department, Brussels, Belgium; Department of Oncology, Ospedali Riuniti, Bergamo; Medical Oncology, Catholic University of the Sacred Heart, Rome; Medical Oncology, Department of Pharmacology, Ospedale San Martino, Genova; Unit of Medical Oncology, Azienda Ospedaliero Universitaria Careggi; Medical Oncology, University of Florence, Florence, Italy; Szent László Hospital, Budapest, Hungary; Medical Oncology Service, Hospital Universitario Reina Sofia, Cordoba; Medical Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain; Hôpital Ambroise Paré, Centre Hospitalier Universitaire Paris Ouest, Boulogne; Service d'Hépato-Gastro-Entérologie and Service D'Oncologie Medicale, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; St Luke's Cancer Centre, Royal Surrey County Hospital, Guildford; Royal Marsden Hospital National Health Service Foundation Trust, London and Surrey, United Kingdom; Third Medical Department with Hematology and Oncology, Private Medical University, Salzburg, Austria; Pfizer, New York, NY; Department of Haematology and Oncology, University Hospital Hamburg, Eppendorf, Germany; and Department of Surgery, Hôpital Cantonal Universitaire Genève, Genève, Switzerland.

Corresponding author: Eric Van Cutsem, MD, PhD, Digestive Oncology Unit, University Hospital Gasthuisberg/Leuven, Herestraat 49, 3000 Leuven, Belgium; e-mail: Eric.VanCutsem{at}uz.kuleuven.ac.be.

Purpose The primary objective of this randomized, multicenter, phase III trial was to investigate whether the addition of irinotecan to the de Gramont infusional fluorouracil (FU)/leucovorin (LV) adjuvant regimen (LV5FU2) would improve disease-free survival (DFS) in patients with stage III colon cancer.

Patients and Methods After curatively intentioned surgery, patients with stage II and III colon cancer were randomly allocated surgery to receive LV5FU2 (LV 200 mg/m² as a 2-hour infusion, followed by FU; as a 400 mg/m² bolus and then a 600 mg/m² continuous infusion over 22 hours, days 1 and 2, every 2 weeks for 12 cycles: de Gramont regimen) with or without irinotecan (180 mg/m² as a 30- to 90-minute infusion, day 1, every 2 weeks). In total, 260 (7.9%) of 3,278 patients received an alternative high-dose infusional FU/LV regimen (Arbeitsgemeinschaft Internische Onkologie regimen) with or without irinotecan.

Results The principal efficacy analysis was based on 2,094 treated patients with stage III disease, randomly allocated in the LV5FU2 strata. After a median follow-up of 66.3 months, the 5-year DFS rate was 56.7% with irinotecan/LV5FU2 and 54.3% with LV5FU2 alone (primary end point: log-rank P = .106). Combining irinotecan with LV5FU2 did not significantly improve overall survival in this patient group compared with LV5FU2 alone (5-year rate 73.6% v 71.3%, respectively; log-rank P = .094). The addition of irinotecan to LV5FU2 was associated with an increased incidence of grade 3 to 4 GI events and neutropenia.

Conclusion Irinotecan added to LV5FU2 as adjuvant therapy did not confer a statistically significant improvement in DFS or overall survival in patients with stage III colon cancer compared with LV5FU2 alone.

Supported by Pfizer.

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

Clinical Trials repository link available JCO.org.

Clinical trial information can be found for the following: NCT00026273 [ClinicalTrials.gov] .

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

Related Article

• Improved Overall Survival With Oxaliplatin, Fluorouracil, and Leucovorin As Adjuvant Treatment in Stage II or III Colon Cancer in the MOSAIC Trial
  Thierry André, Corrado Boni, Matilde Navarro, Josep Tabernero, Tamas Hickish, Clare Topham, Andrea Bonetti, Philip Clingan, John Bridgewater, Fernando Rivera, and Aimery de Gramont
  JCO 2009 27: 3109-3116 [Abstract] [Full Text]

This article has been cited by other articles:

				R. Labianca, B. Nordlinger, G. D. Beretta, A. Brouquet, A. Cervantes, and On behalf of the ESMO Guidelines Working Group Primary colon cancer: ESMO Clinical Practice Guidelines for diagnosis, adjuvant treatment and follow-up Ann. Onc., May 1, 2010; 21(suppl_5): v70 - v77. [Full Text] [PDF]

				G. Gasparini, M. R. D'Andrea, and G. Toffoli Irinotecan in the Adjuvant Treatment of Colon Cancer: Is the Story Finished or Does Personalized Therapy Open New Opportunities? J. Clin. Oncol., April 20, 2010; 28(12): e199 - e199. [Full Text] [PDF]

				S. Tejpar, M. Bertagnolli, F. Bosman, H. J. Lenz, L. Garraway, F. Waldman, R. Warren, A. Bild, D. Collins-Brennan, H. Hahn, et al. Prognostic and Predictive Biomarkers in Resected Colon Cancer: Current Status and Future Perspectives for Integrating Genomics into Biomarker Discovery Oncologist, April 1, 2010; 15(4): 390 - 404. [Abstract] [Full Text] [PDF]

				D. G. Power and J. Feilchenfeldt Irinotecan and mismatch repair deficiency Ann. Onc., February 1, 2010; 21(2): 432 - 433. [Full Text] [PDF]

				A. D. Roth, S. Tejpar, M. Delorenzi, P. Yan, R. Fiocca, D. Klingbiel, D. Dietrich, B. Biesmans, G. Bodoky, C. Barone, et al. Prognostic Role of KRAS and BRAF in Stage II and III Resected Colon Cancer: Results of the Translational Study on the PETACC-3, EORTC 40993, SAKK 60-00 Trial J. Clin. Oncol., January 20, 2010; 28(3): 466 - 474. [Abstract] [Full Text] [PDF]

				P. F. Engstrom, J. P. Arnoletti, A. B. Benson III, Y.-J. Chen, M. A. Choti, H. S. Cooper, A. Covey, R. A. Dilawari, D. S. Early, P. C. Enzinger, et al. Colon Cancer J Natl Compr Canc Netw, September 1, 2009; 7(8): 778 - 831. [Abstract] [PDF]

				M. J. O'Connell Oxaliplatin or Irinotecan As Adjuvant Therapy for Colon Cancer: The Results Are In J. Clin. Oncol., July 1, 2009; 27(19): 3082 - 3084. [Full Text] [PDF]