Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database.

Nadine J. McCleary, Jeffrey A. Meyerhardt, Erin Green, Greg Yothers, Aimery de Gramont, Eric Van Cutsem, Michael O'Connell, Christopher J. Twelves, Leonard B. Saltz, Daniel G. Haller, Daniel J. Sargent

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Abstract

Prior studies have suggested that patients with stage II/III colon cancer receive similar benefit from intravenous (IV) fluoropyrimidine adjuvant therapy regardless of age. Combination regimens and oral fluorouracil (FU) therapy are now standard. We examined the impact of age on colon cancer recurrence and mortality after adjuvant therapy with these newer options. We analyzed 11,953 patients age < 70 and 2,575 age ≥ 70 years from seven adjuvant therapy trials comparing IV FU with oral fluoropyrimidines (capecitabine, uracil, or tegafur) or combinations of fluoropyrimidines with oxaliplatin or irinotecan in stage II/III colon cancer. End points were disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). In three studies comparing oxaliplatin-based chemotherapy with IV FU, statistically significant interactions were not observed between treatment arm and age (P interaction = .09 for DFS, .05 for OS, and .36 for TTR), although the stratified point estimates suggested limited benefit from the addition of oxaliplatin in elderly patients (DFS hazard ratio [HR], 0.94; 95% CI, 0.78 to 1.13; OS HR, 1.04; 95% CI, 0.85 to 1.27). No significant interactions by age were detected with oral fluoropyrimidine therapy compared with IV FU; noninferiority was supported in both age populations. Patients age ≥ 70 years seemed to experience reduced benefit from adding oxaliplatin to fluoropyrimidines in the adjuvant setting, although statistically, there was not a significant effect modification by age, whereas oral fluoropyrimidines retained their efficacy.

Original languageEnglish (US)
Pages (from-to)2600-2606
Number of pages7
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume31
Issue number20
DOIs
StatePublished - Jul 10 2013

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oxaliplatin
Colonic Neoplasms
Databases
Fluorouracil
Disease-Free Survival
irinotecan
Recurrence
Survival
Therapeutics
Tegafur
Uracil
Drug Therapy
Mortality

ASJC Scopus subject areas

  • Medicine(all)

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Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer : findings from the ACCENT database. / McCleary, Nadine J.; Meyerhardt, Jeffrey A.; Green, Erin; Yothers, Greg; de Gramont, Aimery; Van Cutsem, Eric; O'Connell, Michael; Twelves, Christopher J.; Saltz, Leonard B.; Haller, Daniel G.; Sargent, Daniel J.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 31, No. 20, 10.07.2013, p. 2600-2606.

Research output: Contribution to journalArticle

McCleary, NJ, Meyerhardt, JA, Green, E, Yothers, G, de Gramont, A, Van Cutsem, E, O'Connell, M, Twelves, CJ, Saltz, LB, Haller, DG & Sargent, DJ 2013, 'Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database.', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 31, no. 20, pp. 2600-2606. https://doi.org/10.1200/JCO.2013.49.6638
McCleary, Nadine J. ; Meyerhardt, Jeffrey A. ; Green, Erin ; Yothers, Greg ; de Gramont, Aimery ; Van Cutsem, Eric ; O'Connell, Michael ; Twelves, Christopher J. ; Saltz, Leonard B. ; Haller, Daniel G. ; Sargent, Daniel J. / Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer : findings from the ACCENT database. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013 ; Vol. 31, No. 20. pp. 2600-2606.
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AU - Yothers, Greg

AU - de Gramont, Aimery

AU - Van Cutsem, Eric

AU - O'Connell, Michael

AU - Twelves, Christopher J.

AU - Saltz, Leonard B.

AU - Haller, Daniel G.

AU - Sargent, Daniel J.

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N2 - Prior studies have suggested that patients with stage II/III colon cancer receive similar benefit from intravenous (IV) fluoropyrimidine adjuvant therapy regardless of age. Combination regimens and oral fluorouracil (FU) therapy are now standard. We examined the impact of age on colon cancer recurrence and mortality after adjuvant therapy with these newer options. We analyzed 11,953 patients age < 70 and 2,575 age ≥ 70 years from seven adjuvant therapy trials comparing IV FU with oral fluoropyrimidines (capecitabine, uracil, or tegafur) or combinations of fluoropyrimidines with oxaliplatin or irinotecan in stage II/III colon cancer. End points were disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). In three studies comparing oxaliplatin-based chemotherapy with IV FU, statistically significant interactions were not observed between treatment arm and age (P interaction = .09 for DFS, .05 for OS, and .36 for TTR), although the stratified point estimates suggested limited benefit from the addition of oxaliplatin in elderly patients (DFS hazard ratio [HR], 0.94; 95% CI, 0.78 to 1.13; OS HR, 1.04; 95% CI, 0.85 to 1.27). No significant interactions by age were detected with oral fluoropyrimidine therapy compared with IV FU; noninferiority was supported in both age populations. Patients age ≥ 70 years seemed to experience reduced benefit from adding oxaliplatin to fluoropyrimidines in the adjuvant setting, although statistically, there was not a significant effect modification by age, whereas oral fluoropyrimidines retained their efficacy.

AB - Prior studies have suggested that patients with stage II/III colon cancer receive similar benefit from intravenous (IV) fluoropyrimidine adjuvant therapy regardless of age. Combination regimens and oral fluorouracil (FU) therapy are now standard. We examined the impact of age on colon cancer recurrence and mortality after adjuvant therapy with these newer options. We analyzed 11,953 patients age < 70 and 2,575 age ≥ 70 years from seven adjuvant therapy trials comparing IV FU with oral fluoropyrimidines (capecitabine, uracil, or tegafur) or combinations of fluoropyrimidines with oxaliplatin or irinotecan in stage II/III colon cancer. End points were disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). In three studies comparing oxaliplatin-based chemotherapy with IV FU, statistically significant interactions were not observed between treatment arm and age (P interaction = .09 for DFS, .05 for OS, and .36 for TTR), although the stratified point estimates suggested limited benefit from the addition of oxaliplatin in elderly patients (DFS hazard ratio [HR], 0.94; 95% CI, 0.78 to 1.13; OS HR, 1.04; 95% CI, 0.85 to 1.27). No significant interactions by age were detected with oral fluoropyrimidine therapy compared with IV FU; noninferiority was supported in both age populations. Patients age ≥ 70 years seemed to experience reduced benefit from adding oxaliplatin to fluoropyrimidines in the adjuvant setting, although statistically, there was not a significant effect modification by age, whereas oral fluoropyrimidines retained their efficacy.

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