Abstract 3131: Novel multi-gene classifier for prediction of relapse-free survival after FU-based adjuvant chemotherapy for stage III colon cancer: A biomarker study of the ACTS-C trial, a randomized controlled study

Purpose Regular physical activity reduces the risk of developing colon cancer, however, its influence on patients with established disease is unknown. Patients and Methods We conducted a prospective observational study of 832 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial. Patients reported on various recreational physical activities approximately 6 months after completion of therapy and were observed for recurrence or death. To minimize bias by occult recurrence, we excluded patients who experienced recurrence or died within 90 days of their physical activity assessment. Results Compared with patients engaged in less than three metabolic equivalent task (MET) -hours per week of physical activity, the adjusted hazard ratio for disease-free survival was 0.51 (95% CI, 0.26 to 0.97) for 18 to 26.9 MET-hours per week and 0.55 (95% CI, 0.33 to 0.91) for 27 or more MET-hours per week. The adjusted P for trend was .01. Postdiagnosis activity was associated with similar improvements in recurrence-free survival (P for trend = .03) and overall survival (P for trend = .01). The benefit associated with physical activity was not significantly modified by sex, body mass index, number of positive lymph nodes, age, baseline performance status, or chemotherapy received. Moreover, the benefit remained unchanged even after excluding participants who developed cancer recurrence or died within 6 months of activity assessment. Conclusion Beyond surgical resection and postoperative adjuvant chemotherapy for stage III colon cancer, for patients who survive and are recurrence free approximately 6 months after adjuvant chemotherapy, physical activity appears to reduce the risk of cancer recurrence and mortality.

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Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial

Journal of Clinical Oncology ◽

10.1200/jco.2017.76.0355 ◽

2018 ◽

Vol 36 (15) ◽

pp. 1469-1477 ◽

Cited By ~ 54

Author(s):

Thierry André ◽

Dewi Vernerey ◽

Laurent Mineur ◽

Jaafar Bennouna ◽

Jérôme Desrame ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Health Care Providers ◽

Disease Free Survival ◽

Phase Iii ◽

Stage Iii ◽

Care Providers ◽

Free Survival ◽

Stage Iii Colon Cancer ◽

Disease Free

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

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Fluorouracil Plus Leucovorin as Effective Adjuvant Chemotherapy in Curatively Resected Stage III Colon Cancer: Results of the Trial adjCCA-01

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.6.1787 ◽

2001 ◽

Vol 19 (6) ◽

pp. 1787-1794 ◽

Cited By ~ 82

Author(s):

Rainer Porschen ◽

Andreas Bermann ◽

Thomas Löffler ◽

Gregor Haack ◽

Klaus Rettig ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Adjuvant Treatment ◽

Disease Free Survival ◽

Stage Iii ◽

Postoperative Treatment ◽

Free Survival ◽

Stage Iii Colon Cancer ◽

Resected Stage ◽

Disease Free

PURPOSE: Adjuvant postoperative treatment with fluorouracil (5-FU) and levamisole in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrence and improves survival. Biochemical modulation of 5-FU with leucovorin has resulted in increased remission rates in metastatic colorectal cancer, thus reflecting an increased tumor-cell kill. The impact of 5-FU plus leucovorin on survival and tumor recurrence was analyzed in comparison with the effects of 5-FU plus levamisole in the prospective multicentric trial adjCCA-01. PATIENTS AND METHODS: Patients with a curatively resected International Union Against Cancer stage III colon cancer were stratified according to T, N, and G category and randomly assigned to receive one of the two adjuvant treatment schemes: 5-FU 400 mg/m2 body-surface area intravenously in the first chemotherapy course, then 450 mg/m2 × 5 days; 12 cycles, plus leucovorin 100 mg/m2 (arm A), or 5-FU plus levamisole (Moertel scheme; arm B). RESULTS: Six hundred eighty (96.9%) of 702 patients enrolled onto this study were eligible. After a median follow-up time of 46.5 months, the 5-FU plus leucovorin combination significantly improved disease-free survival (P = .037) and significantly decreased overall mortality (P = .0089) in comparison with 5-FU plus levamisole. In a multivariate proportional hazards model, adjuvant chemotherapy emerged as a significant prognostic factor for survival (P = .0059) and disease-free survival (P = .03). Adjuvant treatment with 5-FU plus levamisole as well as with 5-FU plus leucovorin was generally well tolerated; only a minority of patients experienced grade 3 and 4 toxicities. CONCLUSION: After a curative resection of a stage III colon cancer, adjuvant treatment with 5-FU plus leucovorin is generally well tolerated and significantly more effective than 5-FU plus levamisole in reducing tumor relapse and improving survival.

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The impact of dietary patterns on cancer recurrence and survival in patients with stage III colon cancer: Findings from CALGB 89803

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4019 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4019-4019

Author(s):

J. A. Meyerhardt ◽

D. Niedzwiecki ◽

D. Hollis ◽

L. Saltz ◽

W. Willett ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Dietary Patterns ◽

Cancer Recurrence ◽

Dietary Factors ◽

Activity Level ◽

Phase Iii ◽

Stage Iii ◽

Free Survival ◽

Stage Iii Colon Cancer

4019 Background: Dietary factors have been associated with the risk of developing colon cancer; the influence of diet on pts with established disease is unknown. Methods: We conducted a prospective observational study of 1,009 patients with stage III colon cancer enrolled in a phase III adjuvant chemotherapy trial. Patients reported on dietary intake using a food frequency questionnaire during and 6 months after adjuvant chemotherapy. We identified two major dietary patterns, prudent and Western, by factor analysis. The prudent pattern was characterized by higher intake of fruits, vegetables, poultry and fish; the Western pattern by higher intake of red meat, fat, refined grains and desserts. Since there was no difference in efficacy between the 2 treatments, data for all pts were combined and analyzed according to quintiles of each dietary pattern. Patients were followed for cancer recurrence or death. Results: A higher intake of a Western pattern diet after cancer diagnosis was associated with a significantly worsened disease-free survival (DFS). After adjustment for gender, age, T and N stage, body mass index, physical activity level, weight change, baseline performance status, and treatment arm, patients in the highest quintile of Western pattern diet intake experienced a hazard ratio for DFS of 3.15 (95% confidence interval [CI], 1.76–5.63; p trend = <0.0001), compared to those in the lowest quintile. Western pattern diet was associated with a similar detriment in recurrence-free survival (adjusted p trend = 0.001) and overall survival (adjusted p trend = 0.0002). In contrast, prudent pattern diet did not significantly influence cancer recurrence or mortality. Conclusions: Higher intake of a Western pattern diet may increase the risk of recurrence and mortality among patients with stage III colon cancer patients treated with surgery and adjuvant chemotherapy. Further studies are needed to delineate which components of such a diet are most influential. [Table: see text] No significant financial relationships to disclose.

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The Latest Update of Prognostic Factors of Stage III Colon Cancer Who Underwent Curative Operation and Postoperative Adjuvant Chemotherapy

International Surgery ◽

10.9738/intsurg-d-15-00231.1 ◽

2019 ◽

Vol 104 (9-10) ◽

pp. 446-452

Author(s):

Keigo Yokoi ◽

Masanori Naito ◽

Keishi Yamashita ◽

Satoru Ishii ◽

Toshimichi Tanaka ◽

...

Keyword(s):

Colon Cancer ◽

Prognostic Factors ◽

Adjuvant Chemotherapy ◽

Poor Prognosis ◽

Univariate Analysis ◽

Stage Iii ◽

Depth Of Invasion ◽

Postoperative Adjuvant Chemotherapy ◽

Free Survival ◽

Stage Iii Colon Cancer

This study aimed to explore the predicting factor of the poor prognosis of stage III colon cancer. Adjuvant chemotherapy for stage III colon cancer has become popular. However, the choice of the optimal adjuvant chemotherapy regimen still remains unclear. A total of 135 patients with stage III colon cancer, treated with postoperative adjuvant chemotherapy from January 2007 to December 2012 at the Kitasato University East Hospital, were reviewed retrospectively in terms of clinicopathologic characteristics associated with survival and recurrence (median observation: 61 months). We used a multivariate Cox hazards model to identify independent prognostic factors in stage III colon cancer. Of the 135 patients, 38 had recurrence. Five-year overall survival was 83.9%, while 3-year recurrence-free survival was 72.8%. Oxaliplatin-containing adjuvant chemotherapy was almost exclusively applied to stage IIIB colon cancer. Univariate analysis of the negative prognostic factors were N2 (P = 0.0004); operation time (P = 0.0346); tumor size (P = 0.0092); depth of invasion (P = 0.005); histology (P = 0.0403); infiltration type (P < 0.0001); lymphatic permeation (ly3, P = 0.0001); and vascular permeation (v3, P = 0.0005). On multivariate analysis, the independent prognostic factors for relapse-free survival were v3 (P = 0.032) and N2 (P = 0.0216). Combination of the prognostic factors clearly stratified prognosis of stage III colon cancer patients, and those with either factor positive had a poor prognosis despite administration of adjuvant chemotherapy. Both v3 and pN2 may be critical prognostic factors in stage III colon cancer with adjuvant chemotherapy. This information would elucidate areas of concern in the present therapeutic strategy in stage III colon cancer.

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Microsatellite instability status as a predictive marker of clinical outcome from FOLFOX adjuvant chemotherapy in stage III colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.493 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 493-493 ◽

Cited By ~ 1

Author(s):

A. Zaanan ◽

J. Flejou ◽

J. Emile ◽

P. Validire ◽

C. Louvet ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Clinical Outcome ◽

Microsatellite Instability ◽

Adjuvant Treatment ◽

Disease Free Survival ◽

Stage Iii ◽

Rank Test ◽

Free Survival ◽

Stage Iii Colon Cancer

493 Background: The addition of oxaliplatin to 5-fluorouracil (5-FU; FOLFOX regimen) was demonstrated to improve the adjuvant treatment of stage III colon cancer. For patients with microsatellite instability (MSI) tumors, several studies suggested a lack of benefit from 5-FU adjuvant chemotherapy but very little data are available regarding FOLFOX adjuvant therapy. The aim of this study was to further assess the value of MSI status as a marker of clinical outcome from FOLFOX adjuvant chemotherapy in stage III colon cancer. Methods: This multicentric retrospective study included 223 unselected patients with stage III colon cancer treated by FOLFOX adjuvant chemotherapy between 2003 and 2007. MSI status was determined by immunohistochemistry as the absence of MLH1, MSH2 or MSH6 expression. Disease-free survival (DFS) and relapse-free survival (RFS) were analyzed according to the MSI status using Kaplan Meier method and compared by log-rank test. Results: Twenty three tumors (10.3%) were MSI. The rate of 3-year DFS was 88.6% and 76.6% for MSI and MSS groups, respectively (HR=0.64; 95% CI, 0.25 to 1.60; P=0.34). The rate of 3-year RFS was 88.6% and 76.7% for MSI and MSS groups, respectively (HR=0.52; 95% CI, 0.20 to 1.30; P=0.18). Conclusions: A trend toward longer survival was observed for patients with MSI tumors compared with those with MSS tumors but the differences in survival were not significant. Interestingly, DFS at 3-years of patients with stage III MSI tumors treated by FOLFOX was higher in our series (88.6%) than in the largest study published for patients treated by 5-FU-based adjuvant chemotherapy (around 67.5%) or surgery alone (around 62.5%) (Sargent et al, JCO 2010). These observations suggest that adding oxaliplatin to 5-FU re-establishes a benefit of adjuvant treatment in the stage III MSI population. These results should be confirmed by analyzing materials of previously completed trials comparing FOLFOX to 5-FU such as the MOSAIC study. [Table: see text]

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Three versus six months adjuvant oxaliplatin-based chemotherapy for patients with stage III colon cancer: The French participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3500 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3500-3500 ◽

Cited By ~ 4

Author(s):

Thierry Andre ◽

Franck Bonnetain ◽

Laurent Mineur ◽

Jaafar Bennouna ◽

Jérôme Desrame ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Disease Free Survival ◽

Stage Iii ◽

Free Survival ◽

Stage Iii Colon Cancer ◽

Longitudinal Measurements ◽

Kaplan Meier ◽

Study Results

3500 Background: The IDEA international collaboration was established to combine data from 6 randomized trials to assess whether a 3-month (3M) of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) for 3-year disease free survival (DFS) in stage III colon cancer (CC). Methods: French IDEA randomized patients (pts) between 3M and 6M of CT with mFOLFOX6 or XELOX (physician/pts choice). DFS was estimated using the Kaplan–Meier method and described using 3 years DFS rate. Results: Among 2022 randomized pts between May 2009 and May 2014, 2010 (99.4%) received CT and were enrolled in the mITT population: 49.9 and 50.1% in 3M and 6M, respectively. 99.5% of the mITT pts had stage III (N1: 74.9%; N2: 25.2%); median age 63.9 years; mFOLFOX6: 90% and XELOX 10% of pts. DFS median follow-up is 50.2 months. There were 578 DFS events (314 in 3M and 264 in 6M arm) leading to a 3-year DFS rate of 72.1% in the 3M vs. 75.7% in the 6M (HR=1.24; 95%CI 1.05–1.46, p=0.0112). For pts receiving mFOLFOX6, 3-year DFS rate was 72.0% in the 3M vs. 76.3% in the 6M (HR=1.27; 95%CI 1.07–1.51 p=0.0069). 94.2% and 78.0% of pts completed 3 and 6 months of CT, respectively. Median oxaliplatin doses intensity were 96.9% in 3M and 72.1% in 6M (495.0 and 735.1 mg/m2). By considering the neuropathy grade with 15375 neuropathy longitudinal measurements the overall maximal neuropathy grade 0-1/2/3-4 was 63.6/28.5/7.9% in 3M and 33.4/41.3/25.3% in 6M; p<0.0001. At last follow-up assessment, with a median of 43.1 months, final residual grade 2/3-4 neuropathy was 2.1/0.4% in 3M and 5.4/1.3% in 6M; p<0.0001. Conclusions: The IDEA France study, with 90% of patients treated with mFOLFOX6 regimen has shown that 6 months adjuvant treatment is superior to 3 months treatment. IDEA France study results should be considered in line with the international IDEA project that will also be presented at ASCO 2017. Clinical trial information: 2009-010384-16.

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Multivitamin Use Is Not Associated With Cancer Recurrence or Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.0362 ◽

2010 ◽

Vol 28 (28) ◽

pp. 4354-4363 ◽

Cited By ~ 23

Author(s):

Kimmie Ng ◽

Jeffrey A. Meyerhardt ◽

Jennifer A. Chan ◽

Donna Niedzwiecki ◽

Donna R. Hollis ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Recurrence ◽

Disease Free Survival ◽

The United States ◽

Stage Iii ◽

Multivitamin Supplementation ◽

Free Survival ◽

Stage Iii Colon Cancer ◽

Multivitamin Use

Purpose Multivitamin use is widespread in the United States, especially among patients with cancer. However, the influence of multivitamin supplementation on cancer recurrence and death after a curative resection of colon cancer is unknown. Patients and Methods We conducted a prospective, observational study of 1,038 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial. Patients reported on multivitamin use during and 6 months after adjuvant chemotherapy. Patients were observed until March 2009 for disease recurrence and death. To minimize bias by occult recurrence, we excluded patients who recurred or died within 90 days of their multivitamin assessment. Results Among 1,038 patients, 518 (49.9%) reported multivitamin use during adjuvant chemotherapy. Compared with nonusers, the multivariate hazard ratio (HR) for disease-free survival was 0.94 (95% CI, 0.77 to 1.15) for patients who used multivitamins. Similarly, multivitamin use during adjuvant chemotherapy was not significantly associated with recurrence-free survival (multivariate HR, 0.93; 95% CI, 0.75 to 1.15) or overall survival (multivariate HR 0.92; 95% CI, 0.74 to 1.16). Multivitamin use reported 6 months after completion of adjuvant chemotherapy was also not associated with improved patient outcome, and consistent use both during and following adjuvant therapy conferred no benefit. Neither an increasing number of tablets nor increasing duration of use before cancer diagnosis was associated with cancer recurrence or mortality. Multivitamin use also did not improve the rates of grade 3 and higher GI toxicity. Conclusion Multivitamin use during and after adjuvant chemotherapy was not significantly associated with improved outcomes in patients with stage III colon cancer.

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