Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the ACCENT database

Salem, Mohamed E.; Yin, Jun; Goldberg, Richard M.; Pederson, Levi; Wolmark, Norman; Alberts, Steven R.; Taieb, Julien; Marshall, J. L.; Yoshino, Takayuki; Kerr, Rachel; Yothers, Greg; Grothey, Axel; Thewis, André; Gramont, Aimery de; Shi, Qiang

doi:10.1016/j.annonc.2019.12.007

Cited by 25 publications

(27 citation statements)

References 14 publications

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“…They "called into question historical data related to the benefit of FU-based adjuvant therapy in such (stage II) patients". In a third ACCENT database analysis [33], patients did better in the trials including patients between 2004-2009 than in those including patients between 1998-2003, but this was probably explained by better possibilities of tolerating oxaliplatin-containing chemotherapy than reflecting decreased recurrence risks as in the two previous analyses. In 2008, The Memorial Sloan Kettering Cancer Center (MSKCC, www.mskcc.org) published a nomogram describing the risk of recurrence and survival in colon cancer stages I-III based upon patients operated between 1990-2000 [34].…”

Section: Introductionmentioning

confidence: 84%

“…The two retrospective subgroup analyses of patients included in the ACCENT database, revealing better results in more recent compared with the older trials that could be ascribed to fewer recurrences, did not quantify the magnitude of the difference [31,32]. When an old nomogram (by MSKCC) was validated, 7-8 percentage points fewer recurrences in both stage II and III were seen (Table 6) [33].…”

Section: Colon Cancermentioning

confidence: 99%

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Recurrence Risk after Radical Colorectal Cancer Surgery—Less Than before, But How High Is It?

Osterman

Hammarström

Imam

et al. 2020

Cancers

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Adjuvant chemotherapy aims at eradicating tumour cells sometimes present after radical surgery for a colorectal cancer (CRC) and thereby diminish the recurrence rate and prolong time to recurrence (TTR). Remaining tumour cells will lead to recurrent disease that is usually fatal. Adjuvant therapy is administered based upon the estimated recurrence risk, which in turn defines the need for this treatment. This systematic overview aims at describing whether the need has decreased since trials showing that adjuvant chemotherapy provides benefits in colon cancer were performed decades ago. Thanks to other improvements than the administration of adjuvant chemotherapy, such as better staging, improved surgery, the use of radiotherapy and more careful pathology, recurrence risks have decreased. Methodological difficulties including intertrial comparisons decades apart and the present selective use of adjuvant therapy prevent an accurate estimate of the magnitude of the decreased need. Furthermore, most trials do not report recurrence rates or TTR, only disease-free and overall survival (DFS/OS). Fewer colon cancer patients, particularly in stage II but also in stage III, today display a sufficient need for adjuvant treatment considering the burden of treatment, especially when oxaliplatin is added. In rectal cancer, neo-adjuvant treatment will be increasingly used, diminishing the need for adjuvant treatment.

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Section: Introductionmentioning

confidence: 84%

Section: Colon Cancermentioning

confidence: 99%

Recurrence Risk after Radical Colorectal Cancer Surgery—Less Than before, But How High Is It?

Osterman

Hammarström

Imam

et al. 2020

Cancers

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“…In a third pooled analysis of the adjuvant trials performed during the past three decades and included in the ACCENT database [38], patients over age 65 years (not 70 as in the other analyses) benefitted from the addition of oxaliplatin in the trials including patients between 2004-2009 (NASABP C-08, PETACC-8, N0147, AVANT) but not in the trials (MOSAIC, NSABP C-07) which included patients between 1998-2003. In the PETACC-8 trial, randomizing colon cancer stage III patients to FOLFOX ± cetuximab [73], 10% of the patients above age 70 years did worse if they received cetuximab.…”

Section: Treatment With a Fluoropyrimidine And Oxaliplatinmentioning

confidence: 99%

“…Furthermore, in a recent update from the ACCENT database [ 38 ], stage III patients treated with an oxaliplatin/5-fluorouracil (5-FU) regimen (FOLFOX or FLOX) and included during a more recent period (2004–2009) compared with older studies (1998–2003, the MOSAIC trial [ 39 ] and NSABP C-07 using bolus FLOX [ 40 ]) fared better. TTR was significantly better in the new era, hazard ratio; 95% confidence interval (HR; 95% CI 0.83; 0.74–0.92).…”

Section: What Is the Present Need In Elderly Patients?mentioning

confidence: 99%

“…5-FU vs combination with oxaliplatin or oral capecitabine 70 HR 0.77 (0.69–0.85) HR 0.86 (0.69–1.06) p -interact = 0.32 HR 0.78 (0.71–0.86) HR 0.94 (0.78–1.13) p -interact= 0.09 HR 0.83 (0.74–0.92) HR 1.04 (0.85–1.27) p -interact= 0.05 Reduced benefit in elderly, no signs of interaction. Salem et al [ 38 ] 6 trials 1754/6501 FU/Lv vs FOLFOX/FLOX, old (1998–2003) vs new era trials (2004–2009) 65 72% 70% 70–71% 64% 78–80% 99% Patients 65+ years did better when receiving oxaliplatin in new vs old era Taieb et al [ 73 ] 149/2559 FOLFOX4 ± cetuximab 70 HR 1.97 (0.99–3.93) Administering cetuximab to elderly worsened DFS, no gain in younger patients Abbreviations: TTR = time to recurrence; DFS = disease-free survival; OS = overall survival; HR = hazard ratio; FU/Lv = 5-FU/leucovorin; ns = not significant; FOLFOX = 5-fluorouracil/leucovorin/oxaliplatin; FLOX = bolus 5-fluororuracil/leucovorin/oxaliplatin; CAPOX = capecitabine, oxaliplatin, i.v.= intravenous. …”

Section: What Do the Trials Tell Us About The Efficacy Of Adjuvantmentioning

confidence: 99%

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Adjuvant Chemotherapy in Elderly Colorectal Cancer Patients

Glimelius

Osterman

2020

Cancers

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The value of adjuvant chemotherapy in elderly patients has been the subject of many overviews, with opinions varying from “not effective”, since randomized trials have not been performed, to “as effective as in young individuals”, based upon many retrospective analyses of randomized trials that have included patients of all ages. In the absence of randomized trials performed specifically with elderly patients, retrospective analyses demonstrate that the influence on the time to tumour recurrence (TTR) may be the same as in young individuals, but that endpoints that include death for any reason, such as recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS), are poorer in the elderly. This is particularly true if oxaliplatin has been part of the treatment. The need for adjuvant chemotherapy after colorectal cancer surgery in elderly patients is basically the same as that in younger patients. The reduction in recurrence risks may be similar, provided the chosen treatment is tolerated but survival gains are less. Adding oxaliplatin to a fluoropyrimidine is probably not beneficial in individuals above a biological age of approximately 70 years. If an oxaliplatin combination is administered to elderly patients, three months of therapy is in all probability the most realistic goal.

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

Meyerhardt

Shi

Fuchs

et al. 2021

JAMA

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IMPORTANCEAspirin and cyclooxygenase 2 (COX-2) inhibitors have been associated with a reduced risk of colorectal polyps and cancer in observational and randomized studies. The effect of celecoxib, a COX-2 inhibitor, as treatment for nonmetastatic colon cancer is unknown. OBJECTIVE To determine if the addition of celecoxib to adjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) improves disease-free survival in patients with stage III colon cancer.DESIGN, SETTING, AND PARTICIPANTS Cancer and Leukemia Group B (Alliance)/Southwest Oncology Group 80702 was a 2 × 2 factorial design, phase 3 trial conducted at 654 community and academic centers throughout the United States and Canada. A total of 2526 patients with stage III colon cancer were enrolled between June 2010 and November 2015 and were followed up through August 10, 2020.INTERVENTIONS Patients were randomized to receive adjuvant FOLFOX (every 2 weeks) for 3 vs 6 months with or without 3 years of celecoxib (400 mg orally daily; n = 1263) vs placebo (n = 1261). This report focuses on the results of the celecoxib randomization. MAIN OUTCOMES AND MEASURESThe primary end point was disease-free survival, measured from the time of randomization until documented recurrence or death from any cause. Secondary end points included overall survival, adverse events, and cardiovascular-specific events. RESULTSOf the 2526 patients who were randomized (mean [SD] age, 61.0 years [11 years]; 1134 women [44.9%]), 2524 were included in the primary analysis. Adherence with protocol treatment, defined as receiving celecoxib or placebo for more than 2.75 years or continuing treatment until recurrence, death, or unacceptable adverse events, was 70.8% for patients treated with celecoxib and 69.9% for patients treated with placebo. A total of 337 patients randomized to celecoxib and 363 to placebo experienced disease recurrence or died, and with 6 years' median follow-up, the 3-year disease-free survival was 76.3% for celecoxib-treated patients vs 73.4% for placebo-treated patients (hazard ratio [HR] for disease recurrence or death, 0.89; 95% CI, 0.76-1.03; P = .12). The effect of celecoxib treatment on disease-free survival did not vary significantly according to assigned duration of adjuvant chemotherapy (P for interaction = .61). Five-year overall survival was 84.3% for celecoxib vs 81.6% for placebo (HR for death, 0.86; 95% CI, 0.72-1.04; P = .13). Hypertension (any grade) occurred while treated with FOLFOX in 14.6% of patients in the celecoxib group vs 10.9% of patients in the placebo group, and a grade 2 or higher increase in creatinine levels occurred after completion of FOLFOX in 1.7% vs 0.5% of patients, respectively.CONCLUSIONS AND RELEVANCE Among patients with stage III colon cancer, the addition of celecoxib for 3 years, compared with placebo, to standard adjuvant chemotherapy did not significantly improve disease-free survival.

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Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the ACCENT database

Cited by 25 publications

References 14 publications

Recurrence Risk after Radical Colorectal Cancer Surgery—Less Than before, But How High Is It?

Recurrence Risk after Radical Colorectal Cancer Surgery—Less Than before, But How High Is It?

Adjuvant Chemotherapy in Elderly Colorectal Cancer Patients

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

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