Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer

2011 ◽  
Vol 29 (11) ◽  
pp. 1465-1471 ◽  
Author(s):  
Daniel G. Haller ◽  
Josep Tabernero ◽  
Jean Maroun ◽  
Filippo de Braud ◽  
Timothy Price ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Folinic Acid ◽  
Mayo Clinic ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Primary Study ◽  
Primary Analysis ◽  
Stage Iii Colon Cancer

PurposeThis multicenter, randomized trial compared capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil (FU) and folinic acid (FA) as adjuvant therapy for patients with stage III colon cancer.Patients and MethodsPatients who had undergone curative resection were randomly assigned to XELOX (oxaliplatin 130 mg/m2on day 1 plus capecitabine 1,000 mg/m2twice daily on days 1 to 14 every 3 weeks for 24 weeks) or a standard bolus FU/FA adjuvant regimen (Mayo Clinic for 24 weeks or Roswell Park for 32 weeks). The primary study end point was disease-free survival (DFS).ResultsThe intention-to-treat population comprised 1,886 patients; 944 patients were randomly assigned to XELOX and 942 to FU/FA (Mayo Clinic, n = 664; Roswell Park, n = 278). After 57 months of follow-up for the primary analysis, 295 patients (31.3%) in the XELOX group had relapsed, developed a new primary colon cancer, or died compared with 353 patients (37.5%) in the FU/FA group (hazard ratio [HR] for DFS, 0.80; 95% CI, 0.69 to 0.93; P = .0045). The 3-year DFS rate was 70.9% with XELOX and 66.5% with FU/FA. The HR for overall survival (OS) for XELOX compared to FU/FA was 0.87 (95% CI, 0.72 to 1.05; P = .1486). The 5-year OS for XELOX and FU/FA were 77.6% and 74.2%, respectively. Follow-up is ongoing. Preplanned multivariate and subgroup analyses supported the robustness of these findings.ConclusionThe addition of oxaliplatin to capecitabine improves DFS in patients with stage III colon cancer. XELOX is an additional adjuvant treatment option for these patients.

Capecitabine plus oxaliplatin (XELOX) versus bolus 5-fluorouracil/leucovorin (5-FU/LV) as adjuvant therapy for stage III colon cancer: Survival follow-up of study NO16968 (XELOXA).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 388-388 ◽  
Author(s):  
Hans-Joachim Schmoll ◽  
Josep Tabernero ◽  
Jean Alfred Maroun ◽  
Filippo G. De Braud ◽  
Timothy Jay Price ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
Stage Iii Colon Cancer ◽  
Systemic Treatments ◽  
Resected Stage

388 Background: The MOSAIC trial demonstrated that adding oxaliplatin to 5-FU/LV (FOLFOX4) improved 3-year disease-free survival (DFS) compared to infusional and bolus 5-FU/LV as adjuvant therapy in patients (pts) with stage II/III colon cancer [André et al. NEJM 2004]. A significant survival advantage for FOLFOX4 versus 5-FU/LV was not evident until after median duration of follow-up had exceeded 6 years [André et al. JCO 2009]. Study NO16968 demonstrated that XELOX was superior to bolus 5-FU/LV as adjuvant therapy in pts with stage III colon cancer in terms of DFS at 57 months median follow-up (HR 0.80; 95% CI 0.69–0.93; p=0.0045) [Haller et al. JCO 2011]. The difference between treatment groups in overall survival (OS) was not significant at 59 months median follow-up (HR=0.87; p=0.1486). Data from the planned final analysis of NO16968 are presented. Methods: Pts with resected stage III colon cancer were randomized to receive XELOX (8 cycles, 24w) or bolus 5-FU/LV (Mayo Clinic, 6 cycles; 24w or Roswell Park, 4 cycles; 32w). The primary study endpoint was DFS. Secondary endpoints included OS. Results: The ITT population included 1886 pts (XELOX, n=944; 5-FU/LV, n=942). After a median follow-up of 74 months, the HR (XELOX vs 5-FU/LV) for DFS was 0.80 (95% CI 0.69–0.93; p=0.0038). Seven-year DFS rates were 63% for XELOX and 56% for 5-FU/LV. After a median follow-up of 83 months, the HR for OS was 0.83 (95% CI 0.70–0.99; p=0.0367). Absolute 7-year OS rates were 73% with XELOX and 67% with 5-FU/LV. After adjusting for stratification and prognostic variables, HRs remained essentially unchanged for both DFS (0.79; 95% CI 0.68–0.91; p=0.0016) and OS (0.84; 95% CI 0.71–1.00; p=0.0477). Locoregional / systemic treatments after recurrence were given in 230 (24%) XELOX pts and 308 (33%) 5-FU/LV pts. Conclusions: The combination of oxaliplatin and capecitabine improves OS significantly compared with 5-FU/LV in the adjuvant treatment of stage III colon cancer after a median follow-up of 83 months; these data are comparable to those achieved with FOLFOX4 in the MOSAIC trial. XELOX is an effective adjuvant therapy option for pts with resected stage III colon cancer.

scholarly journals Updated 5-year survival and exploratory T x N subset analyses of ACTS-CC trial: a randomised controlled trial of S-1 versus tegafur-uracil/leucovorin as adjuvant chemotherapy for stage III colon cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (6) ◽  
pp. e000428 ◽  
Author(s):  
Tetsuya Kusumoto ◽  
Megumi Ishiguro ◽  
Eiji Nakatani ◽  
Motoki Yoshida ◽  
Tsukasa Inoue ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Controlled Trial ◽  
Disease Free Survival ◽  
Stage Iiib ◽  
Phase Iii ◽  
Stage Iii ◽  
Stage Iii Colon Cancer

ObjectiveAdjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC), a randomised phase III trial, demonstrated that adjuvant therapy with S-1 for stage III colon cancer was non-inferior in 3-year disease-free survival (DFS) to that of tegafur-uracil plus leucovorin (UFT/LV). We updated DFS and overall survival (OS) and performed T x N subset analysisMethodsA total of 1518 patients with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80–120  mg/day on days 1–28 every 42 days, four courses) or UFT/LV (UFT: 300–600  mg/day and LV: 75  mg/day on days 1–28 every 35 days, five courses)ResultsThe 5-year DFS rates of the S-1 and UFT/LV group were 70.2 % and 66.9 %, respectively (HR 0.88; 95%  CI 0.74 to 1.06; p=0.177), and non-inferiority of DFS was reconfirmed with a median of 63.5-month follow-up. The similarity of OS was also confirmed (HR 0.92; 95%  CI 0.72 to 1.17; p=0.488); 5-year OS rates of the S-1 and UFT/LV group were 86.0 % and 84.4 %, respectively. No significant interactions were identified between the major baseline characteristics and DFS of the S-1 and UFT/LV groups, except for histological type; S-1 was more favourable in patients with poorly differentiated adenocarcinoma. Patient outcomes were well separated by TNM-substages (IIIA/IIIB/IIIC). With the patients divided into 20 subsets by T and N factors, the DFS and OS rates of T3 and N1 subset, which accounted for 62 % of stage IIIB patients and 44 % of all studied subjects, were significantly better than those of the other subsets in stage IIIB and similar to those of stage IIIA.ConclusionsAdjuvant therapy of S-1 for stage III colon cancer was reconfirmed to be non-inferior in DFS to those of UFT/LV after long follow-up. No difference in OS was also demonstrated. T3N1 patients might be considered separately from other patients included in stage IIIB because of its favourable outcome.Trial registration numberNCT00660894.

The role of TP, TS, and DPD as potential predictors of outcome following capecitabine plus oxaliplatin (XELOX) versus bolus 5-fluorouracil/leucovorin (5-FU/LV) as adjuvant therapy for stage III colon cancer: Biomarker findings from study NO16968 (XELOXA).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3578-3578
Author(s):  
Hans-Joachim Schmoll ◽  
Josep Tabernero ◽  
Jean Alfred Maroun ◽  
Filippo G. De Braud ◽  
Timothy Jay Price ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Cox Regression ◽  
Dihydropyrimidine Dehydrogenase ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
Cox Regression Analysis ◽  
Stage Iii Colon Cancer

3578 Background: In NO16968, XELOX was superior in terms of disease-free survival (DFS) and overall survival (OS) to bolus 5-FU/LV as adjuvant therapy for stage III colon cancer (Schmoll et al. ASCO GI 2012). Three key enzymes appear to have the potential to predict efficacy and/or safety of fluoropyrimidine-based treatment: thymidine phosphorylase (TP), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD). We evaluated the association between baseline TP, TS and DPD and outcome (DFS and OS). Methods: Pts with stage III colon cancer received either XELOX (8 cycles, 24w) or bolus 5-FU/LV (Mayo Clinic, 6 cycles, 24w; Roswell Park, 4 cycles, 32w). The primary study endpoint was DFS; secondary endpoints included OS. TP, TS and DPD expression levels were determined in formalin-fixed, paraffin-embedded tissues by RT-PCR, and the median used as a cut-off point: high (above median) vs. low (below median). Results: The biomarker population included 498 (26%) of 1886 pts entered (XELOX, n=242; 5-FU/LV, n=256). Baseline demographics, tumor characteristics, cancer history and efficacy (DFS and OS) were similar to those in the main study population. Cox regression analysis for DFS (Table). In the XELOX group pts with low DPD and TP levels and a high TP/DPD ratio appeared to have significantly better DFS; this effect was not observed with 5-FU/LV. Subgroup analysis shows that the difference between XELOX and 5-FU/LV was also higher in pts with low DPD levels. Conclusions: These exploratory findings suggest that tumor DPD and TP RNA levels could be used to predict outcomes of adjuvant treatment with fluoropyrimidine/oxaliplatin combinations, and should be validated prospectively. Analysis of the current dataset is ongoing and further details on potential biomarkers will be available. [Table: see text]

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.

Early postoperative PET-CT in patients with pathological stage III colon cancer may change their outcome: Results from a large single-institution study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15163-e15163
Author(s):  
Assaf Moore ◽  
Irit Ben-Aharon ◽  
Ofer Purim ◽  
Gali Perl ◽  
Olga Ulitsky ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Preoperative Staging ◽  
Prospective Trial ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Pathological Stage ◽  
Stage Iii Colon Cancer ◽  
Postoperative Changes ◽  
Pet Ct

e15163 Background: Staging of patients (pts) with pathological stage III colon cancer (CC) is currently suboptimal; many pts still recur despite an unremarkable preoperative staging. We previously reported that early postoperative PET-CT can alter the stage and management of up to 15% of pts with high risk stage III CC and later reported also encouraging preliminary results in a larger cohort of consecutive pts with stage III CC, in which staging and management were altered in 14.5%. The aim of the current study was to expand the previous one to a larger cohort and to evaluate the actual impact of early postoperative PET-CT on pts outcome. Methods: A Retrospective study of all consecutive pts with stage III CC who were treated at our institution and underwent early postoperative PET-CT between 2007-2016. Demographic and clinicopathological data were retrieved. Statistical analyses were done using standard methods. Results: 348 pts, 166 (47.7%) males, with a median age of 66 years (range, 29-92), were included. Pathological stage was IIIA, IIIB and IIIC in 21(6%), 254 (73%) and 73 (21%) pts, respectively. The median number of lymph nodes examined and of positive ones were 14 (range, 3-54) and 2 (range, 0-32), respectively. High FDG-uptake was noted in 95 (27.3%) pts, including 23 (6.6%) with clear postoperative changes and 18 (5.2%) with a false positive uptake, of whom 6 underwent invasive diagnostic procedures. PET-CT results modified the management of 52 pts (14.9%) who were found to have true positive findings: 44 (12.6%) with overt metastatic disease and 8 (2.3%) with a second primary tumor. At a median follow-up of 45.6 months, the estimated 5y disease-free survival for true stage III pts was 81.9% and the 6y overall survival of the entire cohort was 76.4%. Interestingly, of the 44 pts found to be metastatic, 12 (27.3%) underwent curative treatments and 8 (66.7%) of those remain free of disease, with a median follow-up of 64.7 months. Conclusions: In this large cohort, early postoperative PET-CT changed the staging and management of 14.9% of pts with resected stage III CC, with encouraging outcome results. We are conducting a prospective trial to further evaluate this strategy.

Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, 5-fluorouracil and leucovorin in stage III colon cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10003-10003 ◽  
Author(s):  
M. M. Bertagnolli ◽  
C. C. Compton ◽  
D. Niedzwiecki ◽  
R. S. Warren ◽  
S. Jewell ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Colon Cancers ◽  
Early Results ◽  
The Impact

10003 Background: Colon cancers exhibiting a high level of microsatellite instability (MSI-H) show distinct clinicopathological features, including both better prognosis and reduced response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the impact of adjuvant chemotherapy containing irinotecan in patients with MSI-H colon cancers. Methods: CALGB protocol 89803 randomized 1264 patients with resected stage III colon cancer to receive post-operative 5-FU and leucovorin (LV) with or without irinotecan. Paraffin blocks containing primary tumor and normal tissue were collected. Microsatellite instablility was assessed using a panel of mono- and di-nucleotide markers. Disease free survival (DFS) was measured from trial entry until documented disease progression or death from any cause. A statistical significance level of 0.2 was used in screening to generate hypotheses regarding MSI status and outcome. Median follow-up at analysis was 3.8 years. Overall C89803 showed no advantage for addition of irinotecan to 5-FU/LV. Results: Patients with and without tumor samples analyzed did not differ by treatment, age, gender, primary site, T-stage, differentiation, # positive nodes, or mucinous type. Of 482 tumors analyzed, 75 (16%) demonstrated MSI-H. MSI-H cancers were more likely to be located in the proximal colon (p<0.0001), of high histologic grade (p<0.0001) and mucinous histology (p<0.0001), and also had increased numbers of tumor-containing lymph nodes (mean # positive nodes/case = 3.5 for MSI Low/Stable vs. 4.7 for MSI-H; p = 0.04). At the time of analysis 143 of 482 patients (36%) analyzed experienced tumor recurrence and/or death due to any cause. For patients with MSI-H tumors, DFS was better in those treated with irinotecan in addition to 5-FU/LV (logrank p=0.18). Among patients with MSI Low/Stable tumors there was no difference in DFS between those treated with and without irinotecan (logrank p =0.39). Conclusions: Early results from CALGB protocol 89803 indicate that addition of postoperative irinotecan to 5-FU/LV may improve DFS in patients with stage III colon cancers that exhibit MSI-H. Longer follow-up is required to confirm this finding. [Table: see text]

The prospective French participitation to IDEA (International Duration Evaluation of Adjuvant Chemotherapy) study in stage III colon cancer: Patients’ characteristics and safety analysis of 3 versus 6 months of adjuvant chemotherapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 633-633 ◽  
Author(s):  
Thierry Andre ◽  
Aimery De Gramont ◽  
Laurent Mineur ◽  
Jérôme Desramé ◽  
Roger Faroux ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Peripheral Neuropathy ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Patient Choice ◽  
Stage Iii ◽  
Current Standard ◽  
Stage Iii Colon Cancer ◽  
Grade 3

633 Background: The IDEA international collaboration was established to prospectively combine/analyze data from six randomized trials to assess whether a 3-month course of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy (CT) is non-inferior to the 6-month current standard treatment in stage III colon cancer (CC). The primary endpoint of IDEA was 3-year disease-free survival. The accrual goal for the French IDEA study was 2,000 patients. Methods: French IDEA randomized patients with stage III CC between 3 months (arm A) and 6 months (arm B) of adjuvant CT with modified (m) FOLFOX6 or XELOX (depending on physician/patient choice). Oxaliplatin was stopped in case of persistent neuropathy grade ≥2 with fluoropyrimidines continuation for the planned duration. Toxicity was graded during treatment and follow-up using NCI-CTCAE v3.0. Results: From May 2009 to May 2014, 2,023 patients were randomized in 129 French centers either to arm A (n=1009, 49.9%) or to arm B (n=1014, 50.1%). 2012 (99.5%) patients had stage III disease (N1: 75%; N2: 25%) and 11 patients had stage II (n=2) or stage IV disease (n=9). Median age was 64 years (18-85). 89.4% of patients received mFOLFOX6, 10.1% of patients received XELOX, and 0.5% of patients did not receive any study treatment. Overall, 94.1% and 77.5% of patients completed 3 months (arm A) and 6 months (arm B) of CT, respectively. Median oxaliplatin dose was 500 mg/m2 in arm A and 747 mg/m2in arm B. Toxicity profiles depended on the FU backbone with more grade 3/4 neutropenia on mFOLFOX6 (15.0% vs 6.5%) and more grade 3/4 diarrhea (4.7% vs 8.1%) on XELOX. Grade 2/3-4 peripheral neuropathy was less common in arm A than in arm B (23.2/6% vs 37.9/20.4%). Grade 2/3-4 residual neuropathy for patients with a follow-up of at least 3 years (n=811, median follow-up of 3.91 years) was 2.3/0.5% in arm A vs 3.9/ 2.4% in arm B. At 6 months after randomization, mortality rate was 0.7% (n=7) on arm A and 0.5% (n=5) on arm B. Median follow-up is 2.74 years for the whole population. Conclusions: Both mFOLFOX6 and XELOX were safe. Peripheral neuropathy was lower in arm A than in arm B. Clinical trial information: 2009-010384-16.

Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial

2015 ◽  
Vol 33 (32) ◽  
pp. 3733-3740 ◽  
Author(s):  
Hans-Joachim Schmoll ◽  
Josep Tabernero ◽  
Jean Maroun ◽  
Filippo de Braud ◽  
Timothy Price ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Folinic Acid ◽  
Dihydropyrimidine Dehydrogenase ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Tumor Biomarker ◽  
Stage Iii Colon Cancer ◽  
Biomarker Analysis ◽  
Resected Stage

Purpose To report the final efficacy findings and biomarker analysis from the NO16968 trial comparing bolus fluorouracil/folinic acid (FU/FA) with capecitabine plus oxaliplatin (XELOX) in resected stage III colon cancer. Patients and Methods After curative resection, patients were randomly assigned to receive XELOX, as oxaliplatin 130 mg/m2 on day 1 and capecitabine 1,000 mg/m2 twice daily on days 1 to 14 every 3 weeks, or bolus FU/FA, as the Mayo Clinic or Roswell Park regimens, for 6 months. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS). Results The intention-to-treat population comprised 1,886 patients (XELOX, n = 944; FU/FA, n = 942). Seven-year DFS rates were 63% and 56% in the XELOX and FU/FA groups, respectively (hazard ratio [HR], 0.80; 95% CI, 0.69 to 0.93; P = .004). Seven-year OS rates were 73% and 67% in the XELOX and FU/FA groups, respectively (HR, 0.83; 95% CI, 0.70 to 0.99; P = .04). A total of 68% and 77% of patients who experienced relapse or a new colorectal cancer in the XELOX and FU/FA groups, respectively, received drug treatment for metastatic disease. Four hundred ninety-eight patients consented to the biomarker analysis: 242 in the XELOX group and 256 in the FU/FA group. Low tumor expression of dihydropyrimidine dehydrogenase may be predictive for XELOX efficacy; in the XELOX group, for high versus low dihydropyrimidine dehydrogenase expression levels, DFS HR was 2.45 (95% CI, 1.55 to 3.86; P < .001), and OS HR was 2.75 (95% CI, 1.65 to 4.59; P < .001). In the FU/FA group, no statistically significant associations were observed between any tumor biomarker and outcomes. Conclusion XELOX improved OS compared with bolus FU/FA in patients with resected stage III colon cancer after a median follow-up of almost 7 years. XELOX should be considered a standard adjuvant treatment option in patients with stage III disease. Tumoral dihydropyrimidine dehydrogenase expression is a promising predictive, and potentially, highly clinically relevant, biomarker for XELOX efficacy requiring further prospective evaluation.

scholarly journals Effect of Celecoxib vs Placebo Added to Standard Adjuvant Therapy on Disease-Free Survival Among Patients With Stage III Colon Cancer

JAMA ◽  
2021 ◽  
Vol 325 (13) ◽  
pp. 1277
Author(s):  
Jeffrey A. Meyerhardt ◽  
Qian Shi ◽  
Charles S. Fuchs ◽  
Jeffrey Meyer ◽  
Donna Niedzwiecki ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free
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