Survival Following Recurrence in Stage II and III Colon Cancer: Findings From the ACCENT Data Set

2008 ◽  
Vol 26 (14) ◽  
pp. 2336-2341 ◽  
Author(s):  
Michael J. O'Connell ◽  
Megan E. Campbell ◽  
Richard M. Goldberg ◽  
Axel Grothey ◽  
Jean-François Seitz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
Prognostic Factors ◽  
Adjuvant Therapy ◽  
Adjuvant Treatment ◽  
Stage Ii ◽  
Data Set ◽  
Initial Stage ◽  
Recurrent Colon Cancer ◽  
Therapy Clinical Trial

Purpose This study was undertaken to examine five possible prognostic factors in patients with recurrent stage II and III colon cancer: time from randomization on an adjuvant therapy clinical trial to tumor recurrence (< 1 year, 1 to 2 years, 2 to 3 years, 3 to 4 years, > 4 years), initial stage (II v III), initial adjuvant treatment (fluorouracil [FU]-based v surgery alone), the era in which the patient entered an adjuvant therapy clinical trial (1978 to 1985, 1986 to 1992, 1993 to 1999), and patient age at recurrence. Methods The Adjuvant Colon Cancer End Points (ACCENT) data set was analyzed using univariate and multivariate Cox proportional hazards models, stratified by study. Results 5,722 (32.9%) of 17,381 patients experienced recurrence. Median survival following recurrence was 13.3 months. Time from randomization to recurrence was highly prognostic of survival following recurrence (P < .0001). Longer survival following recurrence was seen in patients with initial stage II versus III disease (P < .0001; 14.3% 6-year overall survival after recurrence in initial stage II patients), patients entered more recently onto trials (P < .0001), and patients initially treated with surgery alone versus FU adjuvant treatment (P = .0005). All relationships were maintained in multivariate models. Conclusion Time from initial treatment to recurrence and initial stage are important prognostic factors in patients with recurrent colon cancer. Survival following recurrence increased modestly from 1978 to 1999. Patients who had a recurrence following adjuvant therapy had poorer prognosis than those who progressed after surgery alone. These prognostic factors may be useful for clinical trial design and treatment decisions in patients with recurrent colon cancer.

scholarly journals Estimating adjuvant treatment effects in Stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real‐world data

2020 ◽  
Vol 146 (11) ◽  
pp. 2968-2978 ◽  
Author(s):  
Gabrielle Jongeneel ◽  
Thomas Klausch ◽  
Felice N. Erning ◽  
Geraldine R. Vink ◽  
Miriam Koopman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
Randomized Clinical Trial ◽  
Adjuvant Treatment ◽  
Real World ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Stage Ii ◽  
Real World Data ◽  
Stage Ii Colon Cancer

Pooled Analysis of Fluorouracil-Based Adjuvant Therapy for Stage II and III Colon Cancer: Who Benefits and by How Much?

2004 ◽  
Vol 22 (10) ◽  
pp. 1797-1806 ◽  
Author(s):  
Sharlene Gill ◽  
Charles L. Loprinzi ◽  
Daniel J. Sargent ◽  
Stephan D. Thomé ◽  
Steven R. Alberts ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Nodal Status ◽  
Stage Ii ◽  
Data Set ◽  
Free Survival ◽  
T Stage ◽  
Disease Free

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.

scholarly journals Benefits and Adverse Events in Younger Versus Older Patients Receiving Adjuvant Chemotherapy for Colon Cancer: Findings From the Adjuvant Colon Cancer Endpoints Data Set

2012 ◽  
Vol 30 (19) ◽  
pp. 2334-2339 ◽  
Author(s):  
Joleen Hubbard ◽  
David M. Thomas ◽  
Greg Yothers ◽  
Erin Green ◽  
Charles Blanke ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Clinical Trials ◽  
Adjuvant Therapy ◽  
Adverse Events ◽  
Older Patients ◽  
Stage Ii ◽  
Phase Iii ◽  
Data Set ◽  
Younger Patients ◽  
Cutoff Points

Purpose Limited data exist regarding the outcomes of adjuvant therapy in younger patients with stage II and III colon cancer. We examined disease-free survival (DFS), overall survival (OS), recurrence-free interval (RFI), and grade 3+ adverse events (AEs) in younger patients in the 33,574 patient Adjuvant Colon Cancer Endpoints Group data set. Patients and Methods Individual patient data from 24 randomized phase III clinical trials were obtained for survival outcomes, which included 10 clinical trials for AE outcomes. Two age-based cutoff points were used to define younger patients: age younger than 40 years and younger than 50 years. Adjuvant therapy benefit analyses were limited to the nine clinical trials in which the investigational chemotherapeutic arm demonstrated benefit. Results One thousand seven hundred fifty-eight patients (5.2%) were younger than 40 years, 5,817 patients (17.3%) were younger than 50 years, and only 299 patients (0.9%) were younger than 30 years. No meaningful differences in sex or stage were noted in younger versus older patients. Younger and older patients did not differ in RFI (age, < 40 years: hazard ratio [HR], 1.0; P = .62 and age < 50 years: HR, 1.02; P = .35). Younger patients (both cutoff points), had longer OS and DFS than older patients. In trials demonstrating adjuvant therapy benefit, similar DFS benefit was observed by age. Younger patients experienced less leukopenia and stomatitis, but more frequent nausea/vomiting. Conclusion Among patients on clinical trials, younger and older patients with stage II and III colon cancer had similar RFI and adjuvant therapy benefit. Younger patients have longer OS and DFS, which is likely primarily because of fewer competing causes of death. Adjuvant therapy is beneficial for colon cancer in patients younger than 50 years who meet typical clinical trial eligibility criteria.

scholarly journals Evidence for Cure by Adjuvant Therapy in Colon Cancer: Observations Based on Individual Patient Data From 20,898 Patients on 18 Randomized Trials

2009 ◽  
Vol 27 (6) ◽  
pp. 872-877 ◽  
Author(s):  
Daniel Sargent ◽  
Alberto Sobrero ◽  
Axel Grothey ◽  
Michael J. O'Connell ◽  
Marc Buyse ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Individual Patient Data ◽  
Patient Data ◽  
Stage Ii ◽  
Recurrence Rates ◽  
Data Set

PurposeLimited data are available on the time course of treatment failures (recurrence and/or death), the nature and duration of adjuvant treatment benefit, and long-term recurrence rates in patients with resected stage II and III colon cancer.MethodsThe data set assembled by the Adjuvant Colon Cancer Endpoints Group, a collection of individual patient data from 18 trials and more than 20,800 patients testing fluorouracil-based adjuvant therapy in patients with stage II or III colon cancer, was analyzed.ResultsA significant overall survival (OS) benefit of adjuvant therapy was consistent over the 8-year follow-up period. The risk of recurrence in patients treated with adjuvant chemotherapy never exceeds that of control patients, signifying that adjuvant therapy cures some patients, as opposed to delaying recurrence. After 5 years, recurrence rates were less than 1.5% per year, and after 8 years, they were less than 0.5% per year. Significant disease-free survival (DFS) benefit from adjuvant chemotherapy was observed in the first 2 years. After 2 years, DFS rates in treated and control patients were not significantly different, and after 4 years, no trend toward benefit was demonstrated. This benefit was primarily driven by patients with stage III disease.ConclusionAdjuvant chemotherapy provides significant DFS benefit, primarily by reducing the recurrence rate, within the first 2 years of adjuvant therapy with some benefit in years 3 to 4, translating into long-term OS benefit. This reflects the curative role of chemotherapy in the adjuvant setting. After 5 years, recurrence rates in patients treated on clinical trials are low, and after 8 years, they are minimal; thus, long-term follow-up for recurrence is of little value.

Survival following recurrence in patients with adjuvant colon cancer: Findings from the 20,800-patient ACCENT dataset

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4009-4009 ◽  
Author(s):  
M. J. O’Connell
Keyword(s):  
Colon Cancer ◽  
Prognostic Factors ◽  
Cancer Survival ◽  
Proportional Hazards ◽  
Selection Effect ◽  
Cox Proportional Hazards ◽  
Stage Ii ◽  
Cox Proportional Hazards Models ◽  
Initial Stage

4009 Purpose: To examine 4 possible prognostic factors in patients (pts) with recurrent (rec) stage II and III colon cancer: time from randomization to rec (< 1 yr, 1–2 yrs 2–3 yrs 3–4 yrs, 4+ yrs), initial stage (II vs III), initial adjuvant treatment (adj rx) (5-FU based vs no rx control), and era pt entered onto study (1978–1985, 1986–1992, 1993–1999). Methods: The Adjuvant Colon Cancer Endpoints (ACCENT) dataset, including individual pt data from 18 trials and over 20,800 pts testing 5-FU based adj rx for pts with stage II and III colon cancer, was analyzed using univariate and multivariate Cox proportional hazards models, stratified by study. The QUASAR trial (Lancet, 2000) was excluded due to non protocol specified follow-up for rec. No data was available on rx subsequent to rec, or tumor characteristics at time of rec. Results: 5,713 of 17,381 (32.9%) of pts experienced rec. Median survival following rec was 13.4 months. Primary results from univariate models are shown in the table . Time from randomization to rec was highly prognostic of survival following rec (p<0.0001); this result was primarily driven by pts with initial stage III disease. Longer survival following rec was also seen in pts with initial stage II vs III disease (p<0.0001), with a 15% 6 year OS in initial stage II pts, pts entered more recently onto trials (p< 0.0001), and pts initially treated with surgery alone vs 5-FU adj rx (p=0.0005). All relationships were maintained in multivariate models. Conclusions: Time from initial rx and initial stage are important prognostic factors in pts with rec colon cancer. Survival following rec increased modestly from 1980–1995 possibly due to improvements in surgery, chemotherapy, supportive care, or unknown selection effects. Pts who rec following adj rx have poorer prognosis than those untreated, which may be a selection effect (only more aggressive tumors escape adj rx), or a sensitivity effect (those without adj rx retain sensitivity to 5-FU in the rec setting). [Table: see text] No significant financial relationships to disclose.

scholarly journals Adjuvant therapy for stages II and III colon cancer: risk stratification, treatment duration, and future directions

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
U. Bender ◽  
Y.S. Rho ◽  
I. Barrera ◽  
S. Aghajanyan ◽  
J. Acoba ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Risk Stratification ◽  
Disease Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Future Directions ◽  
Duration Of Therapy ◽  
Colon Cancer Risk ◽  
Genomic Assays

Background To date, the role of adjuvant systemic therapy in stages ii and iii colon cancer remains a topic of interest and debate. The objective of the present review was to assess the most recent data, specifically addressing methods of risk stratification, duration of therapy, and future directions.Methods PubMed and medline were searched for literature pertinent to adjuvant chemotherapy in either stage ii or stage iii colorectal cancer.Summary Locoregional disease, histopathology, age, laterality, and a number of other biologic and molecular markers appear to have a role in disease risk stratification. The duration of adjuvant therapy for stage iii disease can vary based on risk factors, but use of adjuvant therapy and duration of therapy in stage ii disease remain controversial. Future directions should include genomic assays and improved study design to provide concrete evidence about the duration of adjuvant folfox or capox and about other types of chemotherapy and immunotherapy.

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