Impact of young age on treatment efficacy and safety in advanced colorectal cancer: A pooled analysis of patients from nine first-line phase III chemotherapy trials

Charles Blanke, Brian M. Bot, David M. Thomas, Archie Bleyer, Claus Henning Kohne, Matthew T. Seymour, Aimery De Gramont, Richard M. Goldberg, Daniel J. Sargent

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Purpose: Colorectal cancer predominantly occurs in the elderly, but approximately 5% of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease. Methods: We analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions. Results: A total of 793 patients (13%) were younger than 50 years old; 188 of these patients (3% of total patients) were younger than 40 years old. Grade 3 or worse nausea (10% v 7%; P = .01) was more common, and severe diarrhea (11% v 14%; P = .001) and neutropenia (23% v 26%; P <.001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years. Conclusion: Young age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC.

Original languageEnglish (US)
Pages (from-to)2781-2786
Number of pages6
JournalJournal of Clinical Oncology
Volume29
Issue number20
DOIs
StatePublished - Jul 10 2011
Externally publishedYes

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Colorectal Neoplasms
Safety
Drug Therapy
Combination Drug Therapy
Disease-Free Survival
Neutropenia
Nausea
Diarrhea
Logistic Models
Survival
Fluorouracil
Survival Rate
Clinical Trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Impact of young age on treatment efficacy and safety in advanced colorectal cancer : A pooled analysis of patients from nine first-line phase III chemotherapy trials. / Blanke, Charles; Bot, Brian M.; Thomas, David M.; Bleyer, Archie; Kohne, Claus Henning; Seymour, Matthew T.; De Gramont, Aimery; Goldberg, Richard M.; Sargent, Daniel J.

In: Journal of Clinical Oncology, Vol. 29, No. 20, 10.07.2011, p. 2781-2786.

Research output: Contribution to journalArticle

Blanke, Charles ; Bot, Brian M. ; Thomas, David M. ; Bleyer, Archie ; Kohne, Claus Henning ; Seymour, Matthew T. ; De Gramont, Aimery ; Goldberg, Richard M. ; Sargent, Daniel J. / Impact of young age on treatment efficacy and safety in advanced colorectal cancer : A pooled analysis of patients from nine first-line phase III chemotherapy trials. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 20. pp. 2781-2786.
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abstract = "Purpose: Colorectal cancer predominantly occurs in the elderly, but approximately 5{\%} of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease. Methods: We analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions. Results: A total of 793 patients (13{\%}) were younger than 50 years old; 188 of these patients (3{\%} of total patients) were younger than 40 years old. Grade 3 or worse nausea (10{\%} v 7{\%}; P = .01) was more common, and severe diarrhea (11{\%} v 14{\%}; P = .001) and neutropenia (23{\%} v 26{\%}; P <.001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years. Conclusion: Young age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC.",
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T1 - Impact of young age on treatment efficacy and safety in advanced colorectal cancer

T2 - A pooled analysis of patients from nine first-line phase III chemotherapy trials

AU - Blanke, Charles

AU - Bot, Brian M.

AU - Thomas, David M.

AU - Bleyer, Archie

AU - Kohne, Claus Henning

AU - Seymour, Matthew T.

AU - De Gramont, Aimery

AU - Goldberg, Richard M.

AU - Sargent, Daniel J.

PY - 2011/7/10

Y1 - 2011/7/10

N2 - Purpose: Colorectal cancer predominantly occurs in the elderly, but approximately 5% of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease. Methods: We analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions. Results: A total of 793 patients (13%) were younger than 50 years old; 188 of these patients (3% of total patients) were younger than 40 years old. Grade 3 or worse nausea (10% v 7%; P = .01) was more common, and severe diarrhea (11% v 14%; P = .001) and neutropenia (23% v 26%; P <.001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years. Conclusion: Young age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC.

AB - Purpose: Colorectal cancer predominantly occurs in the elderly, but approximately 5% of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease. Methods: We analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions. Results: A total of 793 patients (13%) were younger than 50 years old; 188 of these patients (3% of total patients) were younger than 40 years old. Grade 3 or worse nausea (10% v 7%; P = .01) was more common, and severe diarrhea (11% v 14%; P = .001) and neutropenia (23% v 26%; P <.001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years. Conclusion: Young age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC.

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