Abstract

A B S T R A C T Purpose Given the cumulative neurotoxicity associated with oxaliplatin, a shorter duration of adjuvant therapy, if equally efficacious, would be advantageous for patients and health-care systems. Methods The Three or Six Colon Adjuvant trial is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III colon cancer to receive 3 months or 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin). Primary end-point is relapse-free survival. Results 3,759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX and 36% CAPOX. Two-thirds were stage III. The median time of follow up was 62 months and 772 relapses or deaths have been observed. The hazard ratio (HR) of the 3 months versus 6 months for relapse/death was 1.14 (95% CI, 0.99 to 1.32; P [for noninferiority] = .514) and the CI crossed the noninferiority limit of 1.20. However, the absolute difference in 3-year RFS was 1.9% (95% CI, -0.7% to 4.4%). Counter-intuitively, while the RFS curves were similar for stage III (HR, 1.07; 95% CI, 0.91 to 1.26) and for CAPOX treated patients (HR, 0.98; 95% CI, 0.77 to 1.26), they were not for stage II and for FOLFOX treated patients, with HR of 1.41 (95% CI, 1.05 to 1.89) and 1.23 (95% CI, 1.03 to 1.46), respectively, favoring the 6 months of treatment. Conclusion The Three or Six Colon Adjuvant trial failed to formally show noninferiority of 3 versus 6 months of treatment to the predefined margin of 20% relative increase. The results depended on the adjuvant regimen and risk. For CAPOX, 3 months were as good as 6 months; for FOLFOX, 6 months added extra benefit. Counter-intuitively, the low-risk patients benefitted more than the high-risk population from the 6-month duration. The choice of regimen and duration should depend on patient characteristics and be balanced against the extra toxicity of longer therapy.

Original languageEnglish
Pages (from-to)1478-1485
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number15
DOIs
Publication statusPublished - May 20 2018

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oxaliplatin
Colonic Neoplasms
Colon
Recurrence
Leucovorin
Therapeutics
Fluorouracil
Multicenter Studies
Capecitabine
Patient Care

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

FOLFOX or CAPOX in stage II to III colon cancer : Efficacy results of the italian three or six colon adjuvant trial. / on behalf of the TOSCA Investigators.

In: Journal of Clinical Oncology, Vol. 36, No. 15, 20.05.2018, p. 1478-1485.

Research output: Contribution to journalArticle

@article{5b235d5af6b0464a99768b38d55f8278,
title = "FOLFOX or CAPOX in stage II to III colon cancer: Efficacy results of the italian three or six colon adjuvant trial",
abstract = "A B S T R A C T Purpose Given the cumulative neurotoxicity associated with oxaliplatin, a shorter duration of adjuvant therapy, if equally efficacious, would be advantageous for patients and health-care systems. Methods The Three or Six Colon Adjuvant trial is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III colon cancer to receive 3 months or 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin). Primary end-point is relapse-free survival. Results 3,759 patients were accrued from 130 Italian sites, 64{\%} receiving FOLFOX and 36{\%} CAPOX. Two-thirds were stage III. The median time of follow up was 62 months and 772 relapses or deaths have been observed. The hazard ratio (HR) of the 3 months versus 6 months for relapse/death was 1.14 (95{\%} CI, 0.99 to 1.32; P [for noninferiority] = .514) and the CI crossed the noninferiority limit of 1.20. However, the absolute difference in 3-year RFS was 1.9{\%} (95{\%} CI, -0.7{\%} to 4.4{\%}). Counter-intuitively, while the RFS curves were similar for stage III (HR, 1.07; 95{\%} CI, 0.91 to 1.26) and for CAPOX treated patients (HR, 0.98; 95{\%} CI, 0.77 to 1.26), they were not for stage II and for FOLFOX treated patients, with HR of 1.41 (95{\%} CI, 1.05 to 1.89) and 1.23 (95{\%} CI, 1.03 to 1.46), respectively, favoring the 6 months of treatment. Conclusion The Three or Six Colon Adjuvant trial failed to formally show noninferiority of 3 versus 6 months of treatment to the predefined margin of 20{\%} relative increase. The results depended on the adjuvant regimen and risk. For CAPOX, 3 months were as good as 6 months; for FOLFOX, 6 months added extra benefit. Counter-intuitively, the low-risk patients benefitted more than the high-risk population from the 6-month duration. The choice of regimen and duration should depend on patient characteristics and be balanced against the extra toxicity of longer therapy.",
author = "{on behalf of the TOSCA Investigators} and Alberto Sobrero and Sara Lonardi and Gerardo Rosati and {Di Bartolomeo}, Maria and Monica Ronzoni and Nicoletta Pella and Mario Scartozzi and Maria Banzi and Zampino, {Maria Giulia} and Felice Pasini and Paolo Marchetti and Maurizio Cantore and Alberto Zaniboni and Lorenza Rimassa and Libero Ciuffreda and Daris Ferrari and Vittorina Zagonel and Evaristo Maiello and Sandro Barni and Eliana Rulli and Roberto Labianca",
year = "2018",
month = "5",
day = "20",
doi = "10.1200/JCO.2017.76.2187",
language = "English",
volume = "36",
pages = "1478--1485",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "15",

}

TY - JOUR

T1 - FOLFOX or CAPOX in stage II to III colon cancer

T2 - Efficacy results of the italian three or six colon adjuvant trial

AU - on behalf of the TOSCA Investigators

AU - Sobrero, Alberto

AU - Lonardi, Sara

AU - Rosati, Gerardo

AU - Di Bartolomeo, Maria

AU - Ronzoni, Monica

AU - Pella, Nicoletta

AU - Scartozzi, Mario

AU - Banzi, Maria

AU - Zampino, Maria Giulia

AU - Pasini, Felice

AU - Marchetti, Paolo

AU - Cantore, Maurizio

AU - Zaniboni, Alberto

AU - Rimassa, Lorenza

AU - Ciuffreda, Libero

AU - Ferrari, Daris

AU - Zagonel, Vittorina

AU - Maiello, Evaristo

AU - Barni, Sandro

AU - Rulli, Eliana

AU - Labianca, Roberto

PY - 2018/5/20

Y1 - 2018/5/20

N2 - A B S T R A C T Purpose Given the cumulative neurotoxicity associated with oxaliplatin, a shorter duration of adjuvant therapy, if equally efficacious, would be advantageous for patients and health-care systems. Methods The Three or Six Colon Adjuvant trial is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III colon cancer to receive 3 months or 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin). Primary end-point is relapse-free survival. Results 3,759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX and 36% CAPOX. Two-thirds were stage III. The median time of follow up was 62 months and 772 relapses or deaths have been observed. The hazard ratio (HR) of the 3 months versus 6 months for relapse/death was 1.14 (95% CI, 0.99 to 1.32; P [for noninferiority] = .514) and the CI crossed the noninferiority limit of 1.20. However, the absolute difference in 3-year RFS was 1.9% (95% CI, -0.7% to 4.4%). Counter-intuitively, while the RFS curves were similar for stage III (HR, 1.07; 95% CI, 0.91 to 1.26) and for CAPOX treated patients (HR, 0.98; 95% CI, 0.77 to 1.26), they were not for stage II and for FOLFOX treated patients, with HR of 1.41 (95% CI, 1.05 to 1.89) and 1.23 (95% CI, 1.03 to 1.46), respectively, favoring the 6 months of treatment. Conclusion The Three or Six Colon Adjuvant trial failed to formally show noninferiority of 3 versus 6 months of treatment to the predefined margin of 20% relative increase. The results depended on the adjuvant regimen and risk. For CAPOX, 3 months were as good as 6 months; for FOLFOX, 6 months added extra benefit. Counter-intuitively, the low-risk patients benefitted more than the high-risk population from the 6-month duration. The choice of regimen and duration should depend on patient characteristics and be balanced against the extra toxicity of longer therapy.

AB - A B S T R A C T Purpose Given the cumulative neurotoxicity associated with oxaliplatin, a shorter duration of adjuvant therapy, if equally efficacious, would be advantageous for patients and health-care systems. Methods The Three or Six Colon Adjuvant trial is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III colon cancer to receive 3 months or 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin). Primary end-point is relapse-free survival. Results 3,759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX and 36% CAPOX. Two-thirds were stage III. The median time of follow up was 62 months and 772 relapses or deaths have been observed. The hazard ratio (HR) of the 3 months versus 6 months for relapse/death was 1.14 (95% CI, 0.99 to 1.32; P [for noninferiority] = .514) and the CI crossed the noninferiority limit of 1.20. However, the absolute difference in 3-year RFS was 1.9% (95% CI, -0.7% to 4.4%). Counter-intuitively, while the RFS curves were similar for stage III (HR, 1.07; 95% CI, 0.91 to 1.26) and for CAPOX treated patients (HR, 0.98; 95% CI, 0.77 to 1.26), they were not for stage II and for FOLFOX treated patients, with HR of 1.41 (95% CI, 1.05 to 1.89) and 1.23 (95% CI, 1.03 to 1.46), respectively, favoring the 6 months of treatment. Conclusion The Three or Six Colon Adjuvant trial failed to formally show noninferiority of 3 versus 6 months of treatment to the predefined margin of 20% relative increase. The results depended on the adjuvant regimen and risk. For CAPOX, 3 months were as good as 6 months; for FOLFOX, 6 months added extra benefit. Counter-intuitively, the low-risk patients benefitted more than the high-risk population from the 6-month duration. The choice of regimen and duration should depend on patient characteristics and be balanced against the extra toxicity of longer therapy.

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U2 - 10.1200/JCO.2017.76.2187

DO - 10.1200/JCO.2017.76.2187

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EP - 1485

JO - Journal of Clinical Oncology

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