Prognostic Significance of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand and Its Receptors in Adjuvantly Treated Stage III Colon Cancer Patients

2006 ◽  
Vol 24 (31) ◽  
pp. 4998-5004 ◽  
Author(s):  
Caroline M. van Geelen ◽  
Jantine L. Westra ◽  
Elisabeth G. de Vries ◽  
Wytske Boersma-van Ek ◽  
Nynke Zwart ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Tumor Necrosis ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free ◽  
Necrosis Factor

Purpose In preclinical models, there is synergism between chemotherapy and recombinant human tumor necrosis factor (TNF) –related apoptosis-inducing ligand (TRAIL) on apoptosis induction in tumor cells. Therefore, the prognostic relevance was analyzed of the expression of TRAIL and its death receptors DR4 and DR5 on disease-free survival and overall survival in stage III colon cancer patients treated with adjuvant chemotherapy. Methods Tissue microarrays were constructed of primary tumor tissue from 376 stage III colon cancer patients treated in a randomized adjuvant chemotherapy study (fluorouracil/levamisole v fluorouracil/levamisole/leucovorin) and stained immunohistochemically for TRAIL, DR4, and DR5. Log-rank tests and Cox proportional hazard analysis, with adjustment for treatment arm, sex, age, N stage, microsatellite instability status, and p53 mutation status, were performed. Results The majority of tumors showed high expression of TRAIL (83%), DR4 (92%), and DR5 (87%). Median follow-up was 43 months. High DR4 expression was associated with worse disease-free survival (odds ratio [OR] = 2.19; 95% CI, 1.06 to 4.53; P = .03), worse overall survival (OR = 2.22; 95% CI,1.03 to 4.81; P = .04) and shorter time to recurrence (P = .02) compared with those with low DR4 expression. TRAIL or DR5 expression had no prognostic value. Conclusion High DR4 expression is associated with worse disease-free and overall survival in stage III adjuvant-treated colon cancer patients. Evaluation of DR4 expression in stage III colon cancer patients may identify a subset requiring more aggressive adjuvant treatment.

scholarly journals MRE11-Deficiency Associated with Improved Long-Term Disease Free Survival and Overall Survival in a Subset of Stage III Colon Cancer Patients in Randomized CALGB 89803 Trial

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e108483 ◽  
Author(s):  
Thomas Pavelitz ◽  
Lindsay Renfro ◽  
Nathan R. Foster ◽  
Amber Caracol ◽  
Piri Welsch ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

Efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for stage III colon cancer patients who underwent curative resection (KSCC1303).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 739-739
Author(s):  
Nobutomo Miyanari ◽  
Yasunori Emi ◽  
Akihito Tsuji ◽  
Kenji Sakai ◽  
Hideaki Anai ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Survival Rate ◽  
Cancer Patients ◽  
Curative Resection ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Stage Iii ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

739 Background: Adjuvant chemotherapy is an accepted treatment method to improve the survival rate of Stage III colon cancer patients. Recently, regimens including oxaliplatin were proven superior to 5-FU only regimens. The purpose of this study was to examine the efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for Stage III colon cancer patients who underwent curative resection. Methods: Colon cancer patients who had undergone curative resection were enrolled in this study. They received oral S-1 40-60 mg twice daily on days 1 to 14 every 3 weeks plus intravenous oxaliplatin 130 mg/m2 on day 1 for 24 months. The primary endpoint was 3-year disease-free survival. The secondary endpoints were the rate of treatment completeness, adverse events, relative dose intensity, disease-free survival and overall survival. Results: Between 2014 February and 2014 December, eighty-nine patients were enrolled in this study. One patient had to be excluded due to ineligibility. The other eighty-eight patients were analyzed. The rate of protocol treatment completeness was 72.3%. Relative dose intensity of S-1 and oxaliplatin were 72 and 76.3, respectively. Hematological severe adverse events (Grade 3/4) were neutropenia (21.3%) and thrombocytopenia (15.7%). The most frequent symptom was diarrhea (Grade 3/4: 5.6%). Six-month disease-free survival rate was 94.3% (95% confidential interval: 86.9-97.6%). Six-month overall survival rate was 98.9% (95% C.I.: 92.2-99.8%). Conclusions: C-SOX for Stage III colon cancer patients who underwent curative resection was safe and feasible. The long-term outcome should be evaluated in future studies. Clinical trial information: 000012618.

scholarly journals Real-World Effectiveness of Adjuvant Oxaliplatin Chemotherapy in Stage III Colon Cancer: A Controlled Interrupted Time Series Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen-Kuan Huang ◽  
Hung-Chih Hsu ◽  
Shu-Hao Chang ◽  
Wen-Chi Chou ◽  
Pei-Hung Chang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Real World ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Interrupted Time Series Analysis ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

Background: The real-world effectiveness of oxaliplatin in stage III colon cancer has not been determined in a large-scale population. We aimed to assess the real-world impact of adjuvant oxaliplatin treatment on the survival of these patients.Methods: Based on Taiwan cancer registry, we evaluated 17,801 patients with resected stage III colon cancer, including 14,168 patients receiving adjuvant chemotherapy and 3,633 not receiving adjuvant chemotherapy as the control group between 2004 and 2014. We used the controlled interrupted time-series analysis to assess the three-year disease-free survival and five-year overall survival rates before (2004–2008) and after (2009–2014) the addition of oxaliplatin.Results: The introduction of oxaliplatin was associated with no significant improvement in the slopes (per half-year) of the three-year disease-free survival rate (0.2%, 95% CI: −1.7∼2.2%) and five-year overall survival rate (0.6%, 95% CI: −1.8∼3%). The patients receiving oxaliplatin-based chemotherapy also showed no significant increase in the slopes (per half-year) of the three-year disease-free survival rate (0.6%, 95% CI: −1.4∼2.6%) and five-year overall survival rate (1%, 95% CI: −1.5∼3.5%). The nonsignificant results were consistent across subgroup analyses of age (<70 vs. ≥70 years), recurrence risk (T1-3 or N1 vs. T4 or N2), and cycle of oxaliplatin use (≤6 vs. >6). However, oxaliplatin-based chemotherapy significantly increased the slope (per half-year) of the five-year OS (2%, 95% CI: 0.2∼3.8%) for patients in the high-risk group (T4 or N2). The present results were robust in several sensitivity analyses.Conclusion: Among real-world patients with stage III colon cancer, the introduction of oxaliplatin does not yield a significant improvement in survival. Future work should identify the subpopulation(s) of patients who benefit significantly from the addition of oxaliplatin.

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

2018 ◽  
Vol 36 (15) ◽  
pp. 1469-1477 ◽  
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.

Efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for treating patients with stage III colon cancer (KSCC1303): final analysis of 3-year disease-free survival

2020 ◽  
Vol 25 (6) ◽  
pp. 1115-1122
Author(s):  
Koji Ando ◽  
◽  
Yasunori Emi ◽  
Nobutomo Miyanari ◽  
Akihito Tsuji ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Disease Free Survival ◽  
Final Analysis ◽  
Stage Iii ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer

2017 ◽  
Author(s):  
Kelly McLeon
Keyword(s):  
Colon Cancer ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Reference Standard ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Study Intervention ◽  
Disease Free

The landmark MOSAIC trial examined whether the addition of oxaliplatin to a postoperative adjuvant treatment regimen of fluorouracil and leucovorin affected disease-free survival from colon cancer. The MOSAIC trial established the efficacy of FOLFOX over 5-FU/LV as adjuvant treatment for stage III colon cancer and established FOLFOX4 as the reference standard for adjuvant treatment for stage III disease. This chapter describes the basics of the study, including funding, year study began, year study was published, study location, who was studied, who was excluded, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, gives a summary and discusses implications, and concludes with a relevant clinical case.

Prognostic impact of body mass index upon cancer recurrence and survival in stage III colon cancer patients from adjuvant chemotherapy trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11088-11088
Author(s):  
F. Sinicrope ◽  
N. R. Foster ◽  
D. J. Sargent ◽  
S. R. Alberts ◽  
M. J. O'Connell
Keyword(s):  
Colon Cancer ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Normal Weight ◽  
Stage Iii ◽  
Obese Patients ◽  
Tumor Site ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

11088 Background: Obesity is associated with an increased risk of colon cancer. However, the influence of body mass index (BMI) upon the prognosis of patients with established colon cancer remains unknown. Methods: We conducted a retrospective study of 1,803 patients with surgically resected stage III colon cancer who were enrolled in five randomized trials of 5-fluorouracil-based adjuvant chemotherapy conducted by the North Central Cancer Treatment Group. Patient height and weight were recorded at study entry and BMI (kg/m2) was calculated and categorized. Cancer recurrence or death were monitored during 5 years of follow-up. The score and likelihood ratio p-values were determined from univariate and multivariate Cox regression models respectively, after stratifying by study. Results: Among stage III colon cancer patients, 19% were obese (BMI 30 kg/m2), 37% were overweight (BMI, 25 to 29.9 kg/m2), 38% were of normal-weight (BMI, 20 to 24.9 kg/m2), and 6% were underweight (BMI < 20 kg/m2). Obese versus normal-weight patients showed higher rates of lymph node (LN) metastasis (>3 LNs; 38% vs. 29%, p <0.01) and tumor site was more likely to be distal versus proximal (52% vs. 45%, p= 0.03). No differences in age, gender, or histologic grade were found. In a univariate analysis, obese patients had significantly worse disease-free survival (DFS) compared with normal-weight patients (hazard ratio 1.25 (95% CI: 1.04 -1.51; p= 0.02). The 5 year DFS rates were 49% in obese patients versus 57% in normal weight subjects. Furthermore, poorer DFS was observed for obese patients after adjusting for age, sex, histologic grade, and tumor site (p= 0.03). Neither overweight nor underweight patients (vs. normal-weight) had significantly different DFS. Analysis of the predictive impact of BMI for 5-FU-based adjuvant therapy is in progress. Conclusions: Obesity (BMI 30 kg/m2) was associated with a greater number of metastatic lymph nodes and poorer disease-free survival in patients with stage III colon cancer, suggesting that obesity influences tumor progression. No significant financial relationships to disclose.

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

2001 ◽  
Vol 19 (6) ◽  
pp. 1787-1794 ◽  
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.

Efficacy findings from a randomized phase III trial of capecitabine plus oxaliplatin versus bolus 5-FU/LV for stage III colon cancer (NO16968): Impact of age on disease-free survival (DFS).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 3521-3521 ◽  
Author(s):  
D. G. Haller ◽  
J. Cassidy ◽  
J. Tabernero ◽  
J. A. Maroun ◽  
F. G. De Braud ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free
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