A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer

Marc Ychou, W. Hohenberger, S. Thezenas, M. Navarro, J. Maurel, C. Bokemeyer, E. Shacham-Shmueli, F. Rivera, C. Kwok-Keung Choi, A. Santoro

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Abstract

Background: Studies indicate that adjuvant 5-fluorouracil (5-FU) with folinic acid (FA) in colorectal cancer patients with completely resectable liver-limited metastases (LMCRC) offers clinical benefit over surgery alone. This phase III trial compared FOLFIRI with simplified 5-FU/FA in this setting. Patients and methods: LMCRC patients were randomized to receive every 14 days, FA, 400 mg/m2 infused over 2 h, followed by 5-FU as a 400 mg/m2 i.v. bolus, followed by continuous 5-FU infusion, 2400 mg/m2 over 46 h (LV5FUs) with or without irinotecan: 180 mg/m2 infusion (FOLFIRI). The primary end point was disease-free survival (DFS); secondary end points included overall survival (OS) and safety. Results: Treated patients (n = 306) were balanced for critical prognostic factors in each arm. Median DFS in patients receiving LV5FUs was 21.6 versus 24.7 months for FOLFIRI [hazard ratio (HR) 0.89, log-rank P = 0.44]. No significant differences were found in OS. A trend was observed for improved DFS in patients receiving FOLFIRI within 42 days of surgery (HR 0.75, P = 0.17). Grade 3/4 toxic effects were more common in patients treated with FOLFIRI versus LV5FUs (47% versus 30%) with neutropenia being most common (23% versus 7%). Conclusion: FOLFIRI in the adjuvant treatment of LMCRC showed no significant improvement in DFS compared with LV5FUs.

Original languageEnglish
Pages (from-to)1964-1970
Number of pages7
JournalAnnals of Oncology
Volume20
Issue number12
DOIs
Publication statusPublished - 2009

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Leucovorin
Fluorouracil
Colorectal Neoplasms
Neoplasm Metastasis
Liver
Disease-Free Survival
irinotecan
Survival
Poisons
Neutropenia
Ambulatory Surgical Procedures
Safety

Keywords

  • 5-fluorouracil
  • Adjuvant treatment
  • Colorectal cancer
  • FOLFIRI
  • Resection of liver metastases

ASJC Scopus subject areas

  • Oncology
  • Hematology

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A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. / Ychou, Marc; Hohenberger, W.; Thezenas, S.; Navarro, M.; Maurel, J.; Bokemeyer, C.; Shacham-Shmueli, E.; Rivera, F.; Kwok-Keung Choi, C.; Santoro, A.

In: Annals of Oncology, Vol. 20, No. 12, 2009, p. 1964-1970.

Research output: Contribution to journalArticle

Ychou, M, Hohenberger, W, Thezenas, S, Navarro, M, Maurel, J, Bokemeyer, C, Shacham-Shmueli, E, Rivera, F, Kwok-Keung Choi, C & Santoro, A 2009, 'A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer', Annals of Oncology, vol. 20, no. 12, pp. 1964-1970. https://doi.org/10.1093/annonc/mdp236
Ychou, Marc ; Hohenberger, W. ; Thezenas, S. ; Navarro, M. ; Maurel, J. ; Bokemeyer, C. ; Shacham-Shmueli, E. ; Rivera, F. ; Kwok-Keung Choi, C. ; Santoro, A. / A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. In: Annals of Oncology. 2009 ; Vol. 20, No. 12. pp. 1964-1970.
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abstract = "Background: Studies indicate that adjuvant 5-fluorouracil (5-FU) with folinic acid (FA) in colorectal cancer patients with completely resectable liver-limited metastases (LMCRC) offers clinical benefit over surgery alone. This phase III trial compared FOLFIRI with simplified 5-FU/FA in this setting. Patients and methods: LMCRC patients were randomized to receive every 14 days, FA, 400 mg/m2 infused over 2 h, followed by 5-FU as a 400 mg/m2 i.v. bolus, followed by continuous 5-FU infusion, 2400 mg/m2 over 46 h (LV5FUs) with or without irinotecan: 180 mg/m2 infusion (FOLFIRI). The primary end point was disease-free survival (DFS); secondary end points included overall survival (OS) and safety. Results: Treated patients (n = 306) were balanced for critical prognostic factors in each arm. Median DFS in patients receiving LV5FUs was 21.6 versus 24.7 months for FOLFIRI [hazard ratio (HR) 0.89, log-rank P = 0.44]. No significant differences were found in OS. A trend was observed for improved DFS in patients receiving FOLFIRI within 42 days of surgery (HR 0.75, P = 0.17). Grade 3/4 toxic effects were more common in patients treated with FOLFIRI versus LV5FUs (47{\%} versus 30{\%}) with neutropenia being most common (23{\%} versus 7{\%}). Conclusion: FOLFIRI in the adjuvant treatment of LMCRC showed no significant improvement in DFS compared with LV5FUs.",
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T1 - A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer

AU - Ychou, Marc

AU - Hohenberger, W.

AU - Thezenas, S.

AU - Navarro, M.

AU - Maurel, J.

AU - Bokemeyer, C.

AU - Shacham-Shmueli, E.

AU - Rivera, F.

AU - Kwok-Keung Choi, C.

AU - Santoro, A.

PY - 2009

Y1 - 2009

N2 - Background: Studies indicate that adjuvant 5-fluorouracil (5-FU) with folinic acid (FA) in colorectal cancer patients with completely resectable liver-limited metastases (LMCRC) offers clinical benefit over surgery alone. This phase III trial compared FOLFIRI with simplified 5-FU/FA in this setting. Patients and methods: LMCRC patients were randomized to receive every 14 days, FA, 400 mg/m2 infused over 2 h, followed by 5-FU as a 400 mg/m2 i.v. bolus, followed by continuous 5-FU infusion, 2400 mg/m2 over 46 h (LV5FUs) with or without irinotecan: 180 mg/m2 infusion (FOLFIRI). The primary end point was disease-free survival (DFS); secondary end points included overall survival (OS) and safety. Results: Treated patients (n = 306) were balanced for critical prognostic factors in each arm. Median DFS in patients receiving LV5FUs was 21.6 versus 24.7 months for FOLFIRI [hazard ratio (HR) 0.89, log-rank P = 0.44]. No significant differences were found in OS. A trend was observed for improved DFS in patients receiving FOLFIRI within 42 days of surgery (HR 0.75, P = 0.17). Grade 3/4 toxic effects were more common in patients treated with FOLFIRI versus LV5FUs (47% versus 30%) with neutropenia being most common (23% versus 7%). Conclusion: FOLFIRI in the adjuvant treatment of LMCRC showed no significant improvement in DFS compared with LV5FUs.

AB - Background: Studies indicate that adjuvant 5-fluorouracil (5-FU) with folinic acid (FA) in colorectal cancer patients with completely resectable liver-limited metastases (LMCRC) offers clinical benefit over surgery alone. This phase III trial compared FOLFIRI with simplified 5-FU/FA in this setting. Patients and methods: LMCRC patients were randomized to receive every 14 days, FA, 400 mg/m2 infused over 2 h, followed by 5-FU as a 400 mg/m2 i.v. bolus, followed by continuous 5-FU infusion, 2400 mg/m2 over 46 h (LV5FUs) with or without irinotecan: 180 mg/m2 infusion (FOLFIRI). The primary end point was disease-free survival (DFS); secondary end points included overall survival (OS) and safety. Results: Treated patients (n = 306) were balanced for critical prognostic factors in each arm. Median DFS in patients receiving LV5FUs was 21.6 versus 24.7 months for FOLFIRI [hazard ratio (HR) 0.89, log-rank P = 0.44]. No significant differences were found in OS. A trend was observed for improved DFS in patients receiving FOLFIRI within 42 days of surgery (HR 0.75, P = 0.17). Grade 3/4 toxic effects were more common in patients treated with FOLFIRI versus LV5FUs (47% versus 30%) with neutropenia being most common (23% versus 7%). Conclusion: FOLFIRI in the adjuvant treatment of LMCRC showed no significant improvement in DFS compared with LV5FUs.

KW - 5-fluorouracil

KW - Adjuvant treatment

KW - Colorectal cancer

KW - FOLFIRI

KW - Resection of liver metastases

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