Fluorouracil and Leucovorin With or Without Irinotecan in Treating Patients Following Surgery for Stage III Colorectal Cancer

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill more tumor cells. PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil and leucovorin with or without irinotecan in treating patients who have undergone surgery for stage III colorectal cancer.

Timeline

Start

2001-01

Primary completion

2004-09

Completion

—

Outcome

Missed primary endpoint

paper 5-year DFS rate was 56.7% with irinotecan/LV5FU2 and 54.3% with LV5FU2 alone (primary end point: log-rank P = .106). PMID 19451425 ↗

paper Irinotecan added to LV5FU2 as adjuvant therapy did not confer a statistically significant improvement in DFS or overall survival PMID 19451425 ↗

Publications

• Background Punt CJ, Buyse M, Kohne CH, Hohenberger P, Labianca R, Schmoll HJ, Pahlman L, Sobrero A, Douillard JY. Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials. J Natl Cancer Inst. 2007 Jul 4;99(13):998-1003. doi: 10.1093/jnci/djm024. Epub 2007 Jun 27.
• Results Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, Dietrich D, Biesmans B, Bodoky G, Barone C, Aranda E, Nordlinger B, Cisar L, Labianca R, Cunningham D, Van Cutsem E, Bosman F. 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. 2010 Jan 20;28(3):466-74. doi: 10.1200/JCO.2009.23.3452. Epub 2009 Dec 14.
• Results Bosman FT, Yan P, Tejpar S, Fiocca R, Van Cutsem E, Kennedy RD, Dietrich D, Roth A. Tissue biomarker development in a multicentre trial context: a feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial. Clin Cancer Res. 2009 Sep 1;15(17):5528-33. doi: 10.1158/1078-0432.CCR-09-0741. Epub 2009 Aug 18.
• Results Roth AD, Tejpar S, Yan P, et al.: Correlation of molecular markers in colon cancer with stage-specific prognosis: results of the translational study on the PETACC 3 - EORTC 40993-SAKK 60-00 trial. [Abstract] American Society of Clinical Oncology 2009 Gastrointestinal Cancers Symposium, 15-17 January 2009, San Francisco, CA. A-288, 2009.
• Results Tejpar S, Bosman F, Delorenzi M, et al.: Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial). [Abstract] J Clin Oncol 27 (Suppl 15): A-4001, 2009.
• Results Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B, Topham C, Tabernero J, Andre T, Sobrero AF, Mini E, Greil R, Di Costanzo F, Collette L, Cisar L, Zhang X, Khayat D, Bokemeyer C, Roth AD, Cunningham D. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009 Jul 1;27(19):3117-25. doi: 10.1200/JCO.2008.21.6663. Epub 2009 May 18.
• Results Roth AD, Yan P, Dietrich D, et al.: Does UGT1A1*28 homozygosity predict for severe toxicity in patients treated with 5-fluorouracil (5-FU)-irinotecan (IRI)? Results of the PETACC 3-EORTC 40993-SAKK 60/00 trial comparing IRI/5-FU/folinic acid (FA) to 5-FU/FA in stage II-III colon cancer. [Abstract] American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium, 25-27 January 2008, Orlando, FL. A-277, 2008.
• Results Roth AD, Yan P, Dietrich D, et al.: Is UGT1A1*28 homozygosity the strongest predictor for severe hematotoxicity in patients treated with 5-fluorouracil (5-FU)-irinotecan (IRI)? Results of the PETACC 3 - EORTC 40993 -SAKK 60/00 trial comparing IRI/5-FU/folinic acid (FA) to 5-FU/FA in stage II- III colon cancer (COC) patients. [Abstract] J Clin Oncol 26 (Suppl 15): A-4036, 2008.
• Results van Cutsem E, Labianca R, Hossfeld D, et al.: Randomized phase III trial comparing infused irinotecan / 5-fluorouracil (5-FU)/folinic acid (IF) versus 5-FU/FA (F) in stage III colon cancer patients (pts). (PETACC 3). [Abstract] J Clin Oncol 23 (Suppl 16): A-LBA8, 3s, 2005.
• Taieb J, Shi Q, Pederson L, Alberts S, Wolmark N, Van Cutsem E, de Gramont A, Kerr R, Grothey A, Lonardi S, Yoshino T, Yothers G, Sinicrope FA, Zaanan A, Andre T. Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an ACCENT pooled analysis of seven studies. Ann Oncol. 2019 Sep 1;30(9):1466-1471. doi: 10.1093/annonc/mdz208.
• Klingbiel D, Saridaki Z, Roth AD, Bosman FT, Delorenzi M, Tejpar S. Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial. Ann Oncol. 2015 Jan;26(1):126-132. doi: 10.1093/annonc/mdu499. Epub 2014 Oct 30.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Irinotecan	Small molecule	180 mg/m2	Intravenous
Background	Leucovorin	Small molecule	200 mg/m2	Intravenous
Background	fluorouracil	Small molecule	400 mg/m2	Intravenous
Background	fluorouracil	Small molecule	600 mg/m2	Intravenous

Indications