Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: Who benefits and by how much?

Sharlene Gill, Charles Lawrence Loprinzi, Daniel J. Sargent, Stephan Thome, Steven Robert Alberts, Daniel G. Haller, Jacqueline Benedetti, Guido Francini, Lois E. Shepherd, Jean Francois Seitz, Roberto Labianca, Wei Chen, Stephen S. Cha, Michael P. Heldebrant, Richard M. Goldberg

Research output: Contribution to journalArticle

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Abstract

Purpose: Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain. Patients and Methods: Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets. Results: Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only for OS. In a multivariate analysis, adjuvant therapy showed a beneficial treatment effect across all subsets. Treatment benefits were consistent across sex, location, age, T-stage, and grade. A significant stage by treatment interaction was present, with treatment benefiting stage III patients to a greater degree than stage II patients. Conclusion: Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade. Model estimates of survival stratified by T stage, nodal status, grade, and age are available at http://www.mayoclinic.com/calcs. This information may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.

Original languageEnglish (US)
Pages (from-to)1797-1806
Number of pages10
JournalJournal of Clinical Oncology
Volume22
Issue number10
DOIs
StatePublished - 2004

Fingerprint

Fluorouracil
Colonic Neoplasms
Survival
Therapeutics
Disease-Free Survival
Levamisole
Leucovorin
Proportional Hazards Models
Multivariate Analysis
Physicians

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer : Who benefits and by how much? / Gill, Sharlene; Loprinzi, Charles Lawrence; Sargent, Daniel J.; Thome, Stephan; Alberts, Steven Robert; Haller, Daniel G.; Benedetti, Jacqueline; Francini, Guido; Shepherd, Lois E.; Seitz, Jean Francois; Labianca, Roberto; Chen, Wei; Cha, Stephen S.; Heldebrant, Michael P.; Goldberg, Richard M.

In: Journal of Clinical Oncology, Vol. 22, No. 10, 2004, p. 1797-1806.

Research output: Contribution to journalArticle

Gill, S, Loprinzi, CL, Sargent, DJ, Thome, S, Alberts, SR, Haller, DG, Benedetti, J, Francini, G, Shepherd, LE, Seitz, JF, Labianca, R, Chen, W, Cha, SS, Heldebrant, MP & Goldberg, RM 2004, 'Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: Who benefits and by how much?', Journal of Clinical Oncology, vol. 22, no. 10, pp. 1797-1806. https://doi.org/10.1200/JCO.2004.09.059
Gill, Sharlene ; Loprinzi, Charles Lawrence ; Sargent, Daniel J. ; Thome, Stephan ; Alberts, Steven Robert ; Haller, Daniel G. ; Benedetti, Jacqueline ; Francini, Guido ; Shepherd, Lois E. ; Seitz, Jean Francois ; Labianca, Roberto ; Chen, Wei ; Cha, Stephen S. ; Heldebrant, Michael P. ; Goldberg, Richard M. / Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer : Who benefits and by how much?. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 10. pp. 1797-1806.
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abstract = "Purpose: Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain. Patients and Methods: Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets. Results: Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only for OS. In a multivariate analysis, adjuvant therapy showed a beneficial treatment effect across all subsets. Treatment benefits were consistent across sex, location, age, T-stage, and grade. A significant stage by treatment interaction was present, with treatment benefiting stage III patients to a greater degree than stage II patients. Conclusion: Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade. Model estimates of survival stratified by T stage, nodal status, grade, and age are available at http://www.mayoclinic.com/calcs. This information may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.",
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T1 - Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer

T2 - Who benefits and by how much?

AU - Gill, Sharlene

AU - Loprinzi, Charles Lawrence

AU - Sargent, Daniel J.

AU - Thome, Stephan

AU - Alberts, Steven Robert

AU - Haller, Daniel G.

AU - Benedetti, Jacqueline

AU - Francini, Guido

AU - Shepherd, Lois E.

AU - Seitz, Jean Francois

AU - Labianca, Roberto

AU - Chen, Wei

AU - Cha, Stephen S.

AU - Heldebrant, Michael P.

AU - Goldberg, Richard M.

PY - 2004

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N2 - Purpose: Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain. Patients and Methods: Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets. Results: Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only for OS. In a multivariate analysis, adjuvant therapy showed a beneficial treatment effect across all subsets. Treatment benefits were consistent across sex, location, age, T-stage, and grade. A significant stage by treatment interaction was present, with treatment benefiting stage III patients to a greater degree than stage II patients. Conclusion: Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade. Model estimates of survival stratified by T stage, nodal status, grade, and age are available at http://www.mayoclinic.com/calcs. This information may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.

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