Semimonthly Versus Monthly Regimen of Fluorouracil and Leucovorin Administered for 24 or 36 Weeks as Adjuvant Therapy in Stage II and III Colon Cancer: Results of a Randomized Trial

2003 ◽  
Vol 21 (15) ◽  
pp. 2896-2903 ◽  
Author(s):  
Thierry André ◽  
Philippe Colin ◽  
Christophe Louvet ◽  
Erik Gamelin ◽  
Olivier Bouche ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Treatment Groups ◽  
Significant Difference ◽  
Grade 3 ◽  
Disease Free

Purpose: This randomized, 2 × 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes’ B2) and III (Dukes’ C) colon cancer. Patients and Methods: LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m2, respectively) as a 2-hour infusion, followed by a 400 mg/m2 FU bolus and 600 mg/m2 of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m2 of FU as a 15-minute infusion. Results: A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P = .74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P = .63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P = .18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P < .001). Conclusion: Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations.

Oxaliplatin Combined With Weekly Bolus Fluorouracil and Leucovorin As Surgical Adjuvant Chemotherapy for Stage II and III Colon Cancer: Results From NSABP C-07

2007 ◽  
Vol 25 (16) ◽  
pp. 2198-2204 ◽  
Author(s):  
J. Philip Kuebler ◽  
H. Samuel Wieand ◽  
Michael J. O'Connell ◽  
Roy E. Smith ◽  
Linda H. Colangelo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Phase Iii ◽  
Wall Thickening ◽  
Free Survival ◽  
Significant Difference ◽  
Grade 3 ◽  
The Impact ◽  
Disease Free

Purpose This phase III clinical trial evaluated the impact on disease-free survival (DFS) of adding oxaliplatin to bolus weekly fluorouracil (FU) combined with leucovorin as surgical adjuvant therapy for stage II and III colon cancer. Patients and Methods Patients who had undergone a potentially curative resection were randomly assigned to either FU 500 mg/m2 intravenous (IV) bolus weekly for 6 weeks plus leucovorin 500 mg/m2 IV weekly for 6 weeks during each 8-week cycle for three cycles (FULV), or the same FULV regimen with oxaliplatin 85 mg/m2 IV administered on weeks 1, 3, and 5 of each 8-week cycle for three cycles (FLOX). Results A total of 2,407 patients (96.6%) of the 2,492 patients randomly assigned were eligible. Median follow-up for patients still alive is 42.5 months. The hazard ratio (FLOX v FULV) is 0.80 (95% CI, 0.69 to 0.93), a 20% risk reduction in favor of FLOX (P < .004). The 3- and 4-year disease-free survival (DFS) rates were 71.8% and 67.0% for FULV and 76.1% and 73.2% for FLOX, respectively. Grade 3 neurosensory toxicity was noted in 8.2% of patients receiving FLOX and in 0.7% of those receiving FULV (P < .001). Hospitalization for diarrhea associated with bowel wall thickening occurred in 5.5% of the patients receiving FLOX and in 3.0% of the patients receiving FULV (P < .01). A total of 1.2% of patients died as a result of any cause within 60 days of receiving chemotherapy, with no significant difference between regimens. Conclusion The addition of oxaliplatin to weekly FULV significantly improved DFS in patients with stage II and III colon cancer. FLOX can be recommended as an effective option in clinical practice.

scholarly journals Oxaliplatin As Adjuvant Therapy for Colon Cancer: Updated Results of NSABP C-07 Trial, Including Survival and Subset Analyses

2011 ◽  
Vol 29 (28) ◽  
pp. 3768-3774 ◽  
Author(s):  
Greg Yothers ◽  
Michael J. O'Connell ◽  
Carmen J. Allegra ◽  
J. Philip Kuebler ◽  
Linda H. Colangelo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Older Patients ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Treatment Groups ◽  
Bowel Project ◽  
Positive Effect ◽  
Disease Free

Purpose The National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trial demonstrated that the addition of oxaliplatin to fluorouracil plus leucovorin (FULV) improved disease-free survival (DFS) in patients with stage II or III colon cancer. This analysis is the first publication of overall survival (OS) for the NSABP C-07 study. We updated DFS and examined both end points in clinically relevant patient subsets. Patients and Methods Other studies have identified patients age 70 or older and those with stage II disease as patient subsets in which oxaliplatin may not be effective. We investigated toxicity as a driver of divergent outcomes in these subsets. Results In all, 2,409 eligible patients with follow-up were randomly assigned to either FULV (FU 500 mg/m2 by intravenous [IV] bolus weekly for 6 weeks; leucovorin 500 mg/m2 IV weekly for 6 weeks of each 8-week cycle for three cycles) or FLOX (FULV plus oxaliplatin 85 mg/m2 IV on days 1, 15, and 29 of each cycle). With 8 years median follow-up, OS was similar between treatment groups (hazard ratio [HR], 0.88; 95% CI, 0.75 to 1.02; P = .08). FLOX remained superior for DFS (HR, 0.82; 95% CI, 0.72 to 0.93; P = .002). The effect of oxaliplatin on OS did not differ by stage of disease (interaction P = .38 for OS; interaction P = 0.37 for DFS) but did vary by age for OS (younger than age 70 v 70+ interaction P = .039). There was a similar trend for DFS (interaction P = .073). Oxaliplatin significantly improved OS in patients younger than age 70 (HR, 0.80; 95% CI, 0.68 to 0.95; P = .013), but no positive effect was evident in older patients. Conclusion Overall, the addition of oxaliplatin to FULV has not been proven to extend OS in this trial, but the DFS effect remained strong. Unplanned subset analyses suggest a significant OS effect of oxaliplatin in patients younger than age 70.

Re-Evaluating Disease-Free Survival as an Endpoint vs Overall Survival in Stage III Adjuvant Colon Cancer Trials

2021 ◽  
Author(s):  
Jun Yin ◽  
Mohamed E Salem ◽  
Jesse G Dixon ◽  
Zhaohui Jin ◽  
Romain Cohen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Surrogate Endpoint ◽  
Free Survival ◽  
A Value ◽  
Deficient Mismatch Repair ◽  
Disease Free

Abstract Background Disease-free survival with a 3-year median follow-up (3-year DFS) was validated as a surrogate for overall survival with a 5-year median follow-up (5-year OS) in adjuvant chemotherapy colon cancer (CC) trials. Recent data show further improvements in OS and survival after recurrence, in patients who received adjuvant FOLFOX. Hence, re-evaluation of the association between DFS and OS and determination of the optimal follow-up duration of OS to aid its utility in future adjuvant trials are needed. Methods Individual patient data from nine randomized studies conducted between 1998 and 2009 were included; three trials tested biologics. Trial-level surrogacy examining the correlation of treatment effect estimates of 3-year DFS with 5 to 6.5-year OS was evaluated using both linear regression (R2WLS) and Copula bivariate (R2Copula) models and reported with 95% confidence intervals (CIs). For R2, a value closer to 1 indicates a stronger correlation. Results Data from a total of 18,396 patients were analyzed (median age = 59 years; 54.0% male), with 54.1% having low-risk tumors (pT1-3 & pN1), 31.6% KRAS mutated, 12.3% BRAF mutated, and 12.4% microsatellite instability high/deficient mismatch repair tumors. Trial level correlation between 3-year DFS and 5-year OS remained strong (R2 =0.82, 95% CI = 0.67 to 0.98; R2 =0.92, 95% CI = 0.83 to 1.00) and increased as the median follow-up of OS extended. Analyses limited to trials that tested biologics showed consistent results. Conclusion Three-year DFS remains a validated surrogate endpoint for 5-year OS in adjuvant CC trials. The correlation was likely strengthened with 6 years of follow-up for OS.

Oxaliplatin/5FU/LV in adjuvant colon cancer: Updated efficacy results of the MOSAIC trial, including survival, with a median follow-up of six years

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4007-4007 ◽  
Author(s):  
A. de Gramont ◽  
C. Boni ◽  
M. Navarro ◽  
J. Tabernero ◽  
T. Hickish ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Disease Free Survival ◽  
Significant Benefit ◽  
Stage Ii ◽  
Free Survival ◽  
Resected Stage ◽  
To Receive ◽  
Disease Free

4007 Background: The MOSAIC study was designed to evaluate the effects of the FOLFOX4 regimen (5-FU/LV + oxaliplatin) on 3- year disease free survival (DFS) probability in patients with stage II and III colon cancer. Methods: Patients (n=2246) with completely resected stage II (40%) or III (60%) colon cancer were randomly assigned to receive 5-FU/LV (LV5FU2) or FOLFOX4 every 2 weeks for 12 cycles. Results: Results for the primary endpoint of the study (for the overall population, with a median follow-up [FU] of 3 years), showed a significant benefit in DFS for the FOLFOX4-treated patients (78.2% vs 72.9%; HR: 0.77, p=0.002) (André et al, NEJM, 2004). Patients were followed beyond the 3-year cut-off for DFS and overall survival (OS) updates. Final DFS, at 5 years FU, are consistent with earlier results (HR: 0.80, p = 0.003). In addition, at a median FU of 6 years, the study demonstrates a significant benefit in OS for the stage III patients. Summary of OS results (median FU 6 years) Long-term safety update shows no increase in the rate of secondary cancer (5.0% in both treatment arms). Conclusions: These results confirm the benefit of the FOLFOX4 regimen in adjuvant colon cancer patients. [Table: see text] No significant financial relationships to disclose.

Overall survival (OS) and updated disease-free survival (DFS) results of the NSABP C-08 trial assessing bevacizumab (B) in stage II and III colon cancer.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 3508-3508 ◽  
Author(s):  
C. J. Allegra ◽  
G. A. Yothers ◽  
M. J. O'Connell ◽  
S. Sharif ◽  
N. J. Petrelli ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Disease Free

Cochrane systematic review and meta-analysis of adjuvant chemotherapy for stage II colon cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3548-3548
Author(s):  
Brandon Matthew Meyers ◽  
Humaid Obaid Al-Shamsi ◽  
Alvaro Tell Figueredo
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Cochrane Systematic Review ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free

3548 Background: Colon cancer is potentially curable by surgery in the early stages of the disease. Adjuvant chemotherapy improves disease-free and overall survival in patients with stage III disease, but the magnitude of benefit in stage II colon cancer is less clear. A previous Cochrane systematic review and meta-analysis (SR/MA) found improved disease-free, but not overall survival (Figueredo et al., 2008). An updated SR/MA was performed to determine the effects of adjuvant chemotherapy on disease-free and overall survival in patients with stage II colon cancer. Methods: Relevant databases (MEDLINE, EMBASE, and Cochrane) were independently searched by all authors, using the same search strategy employed in the original study (1/1988 to 9/2012). Randomized trials containing data on stage II colon cancer patients undergoing adjuvant 5-fluorouracil (5FU) chemotherapy versus observation were included. Pooled results were expressed as hazard ratios (HR) whenever possible, or risk ratios (RR), with 95% confidence intervals (95%CI) using a random effects model. Results: Seven studies were identified, and included in the final SR/MA. Six of the 7 studies were included in the disease-free survival analysis (n=4587). Adjuvant 5FU was associated with better disease-free survival (RR 0.84 (95%CI 0.75-0.94)). All 7 studies (n=5353) were included in the overall survival analysis showing an improvement with adjuvant 5FU (HR 0.87 (95%CI 0.78-0.97)). There was no evidence of heterogeneity across the studies (I2 = 0% for all analyses). Conclusions: In stage II colon cancer, adjuvant 5FU chemotherapy statistically improves both disease-free and overall survival. Our SR/MA demonstrates, for the first time, an overall survival advantage with adjuvant chemotherapy in stage II colon cancer.

Adjuvant Therapy for Stage II Colon Cancer: A Systematic Review From the Cancer Care Ontario Program in Evidence-Based Care’s Gastrointestinal Cancer Disease Site Group

2004 ◽  
Vol 22 (16) ◽  
pp. 3395-3407 ◽  
Author(s):  
Alvaro Figueredo ◽  
Manya L. Charette ◽  
Jean Maroun ◽  
Melissa C. Brouwers ◽  
Lisa Zuraw
Keyword(s):  
Systematic Review ◽  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Therapy ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free

Purpose To develop a systematic review that would address the following question: Should patients with stage II colon cancer receive adjuvant therapy? Methods A systematic review was undertaken to locate randomized controlled trials comparing adjuvant therapy to observation. Results Thirty-seven trials and 11 meta-analyses were included. The evidence for stage II colon cancer comes primarily from a trial of fluorouracil plus levamisole and a meta-analysis of 1,016 patients comparing fluorouracil plus folinic acid versus observation. Neither detected an improvement in disease-free or overall survival for adjuvant therapy. A recent pooled analysis of data from seven trials observed a benefit for adjuvant therapy in a multivariate analysis for both disease-free and overall survival. The disease-free survival benefits appeared to extend to stage II patients; however, no P values were provided. A meta-analysis of chemotherapy by portal vein infusion has also shown a benefit in disease-free and overall survival for stage II patients. A meta-analysis was conducted using data on stage II patients where data were available (n = 4,187). The mortality risk ratio was 0.87 (95% CI, 0.75 to 1.01; P = .07). Conclusion There is preliminary evidence indicating that adjuvant therapy is associated with a disease-free survival benefit for patients with stage II colon cancer. These benefits are small and not necessarily associated with improved overall survival. Patients should be made aware of these results and encouraged to participate in active clinical trials. Additional investigation of newer therapies and more mature data from the presently available trials should be pursued.

scholarly journals 15-year Follow-up of Comparing Mastoscopic and Conventional Axillary Dissection in Breast Cancer: A Multicentres, Randomized Controlled Trial

2020 ◽  
Author(s):  
Chengyu Luo ◽  
Guang Cao ◽  
wenbin Guo ◽  
Jie Yang ◽  
Qiuru Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Axillary Lymph ◽  
Term Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Disease Free

Abstract Backgroud: Longer follow-up was necessary to testify the exact value of mastoscopic axillary lymph node dissection (MALND).Methods：From January 1, 2003 to December 31, 2005,1027 patients with operable breast cancer were randomly assigned to two groups: MALND and CALND. 996 eligible patients were enrolled. The end points are disease free survival and overall survival.Results：The final cohort of 996 patients was followed for an average of 184 months. The distribution of all events was fairly similar between two groups of patients. The incidence of local in-breast events did not differ in a significant manner between two cohorts. Similarly, the rate of distant metastases was not significantly different with 30.0% in MLND and 32.6% in CALND. And no significant difference was observed in other primary tumor between two groups (p=0.46). Patients who remain alive with no event comprise a total of 37.2% in MALND and 35.4% in CALND. Other primary cancers and deaths from other causes were distributed equally between two groups. The 15-year disease-free survival rates were41.1 percent for the MALND group and 39.6 percent for the CALND group (p=0.79). MALND was found to be not inferior for overall survival (P =0.54). The 15-year overall survival rates were 49.5 percentafter MALND and 51.2 percentafter CALND (p=0.86). Probability of overall survival was not significantly different between two groups.Conclusions：MALND does not increase unfavorable events, and also does not affect the long-term survival of patients. Therefore, MALND should be one of the preferred approaches for breast cancer surgery.

scholarly journals Bevacizumab in Stage II-III Colon Cancer: 5-Year Update of the National Surgical Adjuvant Breast and Bowel Project C-08 Trial

2013 ◽  
Vol 31 (3) ◽  
pp. 359-364 ◽  
Author(s):  
Carmen J. Allegra ◽  
Greg Yothers ◽  
Michael J. O'Connell ◽  
Saima Sharif ◽  
Nicholas J. Petrelli ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
End Point ◽  
Bowel Project ◽  
Modified Folfox6 ◽  
Disease Free

PurposeThe National Surgical Adjuvant Breast and Bowel Project trial C-08 was designed to investigate the safety and efficacy of adding bevacizumab to fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) for the adjuvant treatment of patients with stage 2-3 colon cancer. Our report summarizes the primary and secondary end points of disease-free and overall survival, respectively, with 5 years median follow-up time.Patients and MethodsPatients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus bevacizumab (5 mg/kg) once every 2 weeks for a 12-month period (experimental group). The primary end point of the study was disease-free survival (DFS) and overall survival (OS) was a secondary end point.ResultsOf 2,673 analyzed patients, demographic factors were well-balanced by treatment. With a median follow-up of 5 years, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.93; 95% CI, 0.81 to 1.08; P = .35). Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 1.25-year landmark (time-by-treatment interaction P value <.0001). The secondary end point of OS was no different between the two study arms for all patients (HR, 0.95; 95% CI, 0.79 to 1.13; P = .56) and for those with stage 3 disease (HR, 1.0; 95% CI, 0.83 to 1.21; P = .99).ConclusionBevacizumab for 1 year with modified FOLFOX6 does not significantly prolong DFS or OS in stage 2-3 colon cancer. We observed no evidence of a detrimental effect of exposure to bevacizumab. A transient effect on disease-free survival was observed during bevacizumab exposure in the study's experimental arm.

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