Duration of FOLFOX adjuvant chemotherapy in high-risk stage II and stage III colon cancer with deficient DNA mismatch repair.

4075 Background: In the IDEA collaboration, noninferiority was not confirmed for 3 months versus 6 months of FOLFOX adjuvant chemotherapy among patients with high-risk stage II and stage III colon cancer (CC). Patients with deficient DNA mismatch repair (dMMR) have a good prognosis, but for whom, whether limiting the duration of adjuvant therapy will compromise oncologic outcomes remains undefined. We evaluated the impact of 3 months of FOLFOX adjuvant chemotherapy or surgery alone in comparison with 6 months of FOLFOX on disease-free survival (DFS) in dMMR CC patients. Methods: This retrospective study included all consecutive patients who underwent curative surgical resection for high-risk stage II or III dMMR CC between May, 2011 and July, 2019. Prognostic factors were analyzed using Cox models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results: A total of 242 dMMR CC patients were included (43.4% high-risk stage II, 56.6% stage III). The patients received 6 months of FOLFOX adjuvant chemotherapy (n = 66; median cycles [rang] = 12 [10-12]), 3 months of FOLFOX (n = 87; median cycles [rang] = 6 [4-8]), or surgery alone (n = 89). Three groups were generally well balanced, although more patients with stage III were in the 6-month therapy group (74.2%), compared with the 3-month therapy group (57.5%) and the surgery alone group (42.7%). As compared with 6 months of FOLFOX adjuvant chemotherapy in the overall population, 3 months therapy reduced DFS in multivariable analysis (HR, 2.78; 95CI, 1.18 to 6.47; P = 0.02), similar to surgery alone (HR, 2.30; 95CI, 0.99 to 5.38; P = 0.05). In the subgroup analysis, a therapy duration of 6 months was statistically superior to a duration of 3 months only in the patients with stage III, with a 3-year rate of DFS of 86.2% versus 70.8% (HR, 3.06; 95% CI, 1.14 to 8.19; P = 0.026). Conclusions: This study supports the 6-month duration of FOLFOX adjuvant chemotherapy in stage III dMMR CC.

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Role of Deficient DNA Mismatch Repair Status in Patients With Stage III Colon Cancer Treated With FOLFOX Adjuvant Chemotherapy

JAMA Oncology ◽

10.1001/jamaoncol.2017.2899 ◽

2018 ◽

Vol 4 (3) ◽

pp. 379 ◽

Cited By ~ 44

Author(s):

Aziz Zaanan ◽

Qian Shi ◽

Julien Taieb ◽

Steven R. Alberts ◽

Jeffrey P. Meyers ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Mismatch Repair ◽

Dna Mismatch Repair ◽

Stage Iii ◽

Dna Mismatch ◽

Stage Iii Colon Cancer ◽

Mismatch Repair Status

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Duration of FOLFOX Adjuvant Chemotherapy in High-Risk Stage II and Stage III Colon Cancer With Deficient Mismatch Repair

Frontiers in Oncology ◽

10.3389/fonc.2020.579478 ◽

2020 ◽

Vol 10 ◽

Author(s):

Huabin Hu ◽

Zehua Wu ◽

Chao Wang ◽

Yan Huang ◽

Jianwei Zhang ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Propensity Score ◽

Mismatch Repair ◽

Therapy Group ◽

Stage Ii ◽

Stage Iii ◽

Deficient Mismatch Repair ◽

The Impact

BackgroundWe evaluated the impact of 3 months of mFOLFOX6 adjuvant chemotherapy or surgery alone in comparison with 6 months of mFOLFOX6 on disease-free survival (DFS) in deficient mismatch repair (dMMR) colon cancer (CC) patients.MethodsThis retrospective study identified a cohort of patients with high-risk stage II and III dMMR CC who underwent curative surgery between May 2011 and July 2019. DFS was compared using the Kaplan-Meier survival methods and Cox proportional hazards models. Propensity-score matching was performed to reduce imbalance in baseline characteristics.ResultsA total of 242 dMMR CC patients were identified; 66 patients received 6 months of mFOLFOX6, 87 patients received 3 months of mFOLFOX6, and 89 patients were treated with surgery alone. The 3-year DFS rate was 72.8% in 3-month therapy group and 86.1% in 6-month therapy group, with a hazard ratio (HR) of 2.78 (95CI%, 1.18 to 6.47; P= 0.019). The difference in DFS between surgery alone group and 6-month therapy group was also observed but was nonsignificant (HR= 2.30, 95%CI, 0.99 to 5.38; P=0.054). The benefit of 6-month therapy in DFS compared with 3-month therapy group was pronounced for patients with stage III (HR=2.81, 95%CI, 1.03 to 7.67; P=0.044) but not for high-risk stage II patients. Propensity score matched analysis confirmed a DFS benefit in the 6-month therapy group.ConclusionThis study suggested that a 6-month duration of mFOLFOX6 adjuvant chemotherapy in dMMR CC patients may be associated with improved DFS compared with 3-month therapy, particularly in patients with stage III. The observational nature of the study implies caution should be taken in the interpretation of these results.

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Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline

Current Oncology ◽

10.3747/co.23.3330 ◽

2016 ◽

Vol 23 (6) ◽

pp. 418 ◽

Cited By ~ 15

Author(s):

B.M. Meyers ◽

R. Cosby ◽

F. Quereshy ◽

D. Jonker

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Practice Guideline ◽

Stage Ii ◽

Stage Iii ◽

Cochrane Library ◽

Stage Iii Colon Cancer ◽

Resected Stage ◽

Stage Ii Colon Cancer

Background Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario’s Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken.Methods Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline.Results Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer.Conclusions Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)–based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without “high-risk” features should not receive adjuvant chemotherapy. For patients with “high-risk” features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer.

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Association of Obesity With DNA Mismatch Repair Status and Clinical Outcome in Patients With Stage II or III Colon Carcinoma Participating in NCCTG and NSABP Adjuvant Chemotherapy Trials

Journal of Clinical Oncology ◽

10.1200/jco.2011.39.2563 ◽

2012 ◽

Vol 30 (4) ◽

pp. 406-412 ◽

Cited By ~ 30

Author(s):

Frank A. Sinicrope ◽

Nathan R. Foster ◽

Harry H. Yoon ◽

Thomas C. Smyrk ◽

George P. Kim ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Mismatch Repair ◽

Dna Mismatch Repair ◽

Disease Free Survival ◽

Stage Ii ◽

Prognostic Impact ◽

Obese Patients ◽

Tumor Site ◽

Dna Mismatch

Purpose Although the importance of obesity in colon cancer risk and outcome is recognized, the association of body mass index (BMI) with DNA mismatch repair (MMR) status is unknown. Patients and Methods BMI (kg/m2) was determined in patients with TNM stage II or III colon carcinomas (n = 2,693) who participated in randomized trials of adjuvant chemotherapy. The association of BMI with MMR status and survival was analyzed by logistic regression and Cox models, respectively. Results Overall, 427 (16%) tumors showed deficient MMR (dMMR), and 630 patients (23%) were obese (BMI ≥ 30 kg/m2). Obesity was significantly associated with younger age (P = .021), distal tumor site (P = .012), and a lower rate of dMMR tumors (10% v 17%; P < .001) compared with normal weight. Obesity remained associated with lower rates of dMMR (odds ratio, 0.57; 95% CI, 0.41 to 0.79; P < .001) after adjusting for tumor site, stage, sex, and age. Among obese patients, rates of dMMR were lower in men compared with women (8% v 13%; P = .041). Obesity was associated with higher recurrence rates (P = .0034) and independently predicted worse disease-free survival (DFS; hazard ratio [HR], 1.37; 95% CI, 1.14 to 1.64; P = .0010) and overall survival (OS), whereas dMMR predicted better DFS (HR, 0.59; 95% CI, 0.47 to 0.74; P < .001) and OS. The favorable prognosis of dMMR was maintained in obese patients. Conclusion Colon cancers from obese patients are less likely to show dMMR, suggesting obesity-related differences in the pathogenesis of colon cancer. Although obesity was independently associated with adverse outcome, the favorable prognostic impact of dMMR was maintained among obese patients.

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Three- versus six-month adjuvant FOLFOX or CAPOX for high-risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project

Annals of Oncology ◽

10.1093/annonc/mdz193 ◽

2019 ◽

Vol 30 (8) ◽

pp. 1304-1310 ◽

Cited By ~ 6

Author(s):

J. Souglakos ◽

I. Boukovinas ◽

S. Kakolyris ◽

S. Xynogalos ◽

N. Ziras ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Research Group ◽

Stage Ii ◽

Stage Iii ◽

Stage Iii Colon Cancer ◽

Oncology Research

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Germline variants and clinical outcomes of high-risk stage II and stage III colon cancer patients treated with oxaliplatin and fluoropyrimidines adjuvant chemotherapy: a pharmacogenetic ancillary study to TOSCA trial

Annals of Oncology ◽

10.1093/annonc/mdx422.002 ◽

2017 ◽

Vol 28 ◽

pp. vi3-vi4

Author(s):

A. Ruzzo ◽

F. Galli ◽

E. Rulli ◽

S. Lonardi ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Clinical Outcomes ◽

Stage Ii ◽

Stage Iii ◽

Germline Variants ◽

Stage Iii Colon Cancer ◽

Ancillary Study

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Adjuvant chemotherapy for stage II and stage III colon cancer—What is happening in routine practice?

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15046 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15046-e15046

Author(s):

S. Ananda ◽

S. Kosmider ◽

L. Lim ◽

F. Barnett ◽

J. Desai ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Stage Ii ◽

Stage Iii ◽

Routine Practice ◽

Younger Patients ◽

Stage Iii Colon Cancer ◽

Co Morbidity ◽

Practice Methods

e15046 Background: Randomised studies have defined adjuvant chemotherapy as standard treatment for stage III colon cancer (SIIICC), with multiple options available. For stage II (SII) disease, the selection of patients for adjuvant treatment remains controversial. There remains limited data on clinician decision making regarding adjuvant chemotherapy in routine clinical practice. Methods: A review of patients treated with SII & IIICC at 4 hospitals, utilising data from BioGrid Australia, where clinician choice and rationale were prospectively documented. Results: 372 patients (37%) with SII and 307 (30%) with SIIICC were identified from 1015 CC patients treated from January 2003 till November 2008. Median age was 68 years, 51% were male; 49% female. 66 (25%) of patients with SIIICC were not offered chemotherapy, predominantly due to advanced age or co-morbidity. Since oxaliplatin and capecitabine became widely available in 2005, 66% of treated patients have received oxaliplatin based therapy, 15% bolus 5-FU alone and 19% capecitabine. For SII disease, overall 81 (26%) pts received adjuvant chemotherapy. Age was the dominant influence on treatment choice with 41% aged 70 (p<0.001) receiving treatment. Patients with high risk features were also more likely to receive adjuvant therapy. (p= 0.006 for those with lymphovascular invasion and p= 0.0068 for those with T4 tumours). Dose reductions and completion rates were similar for SII and III disease, and for older and younger patients. Conclusions: Over 25% of patients with SIIICC do not receive adjuvant chemotherapy in routine practice, with physicians basing non-treatment recommendations predominantly on patient age and co-morbidity. Where treatment is used, oxaliplatin-based therapy is the dominant regimen, except in older patients. In SIICC, adjuvant chemotherapy is used in one in four patients, more frequently in younger patients and those with high risk features. No significant financial relationships to disclose.

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Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: The efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3500 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3500-3500

Author(s):

Ioannis Sougklakos ◽

Ioannis Boukovinas ◽

Spyros Xynogalos ◽

Stylianos Kakolyris ◽

Nikolaos Ziras ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Disease Free Survival ◽

Stage Ii ◽

Stage Iii ◽

Free Survival ◽

Stage Iii Colon Cancer ◽

Oncology Research

3500 Background: The IDEA aimed to investigate whether a 3-month (3M) of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) in 3-year disease free survival (DFS) in stage high risk stage II and in stage III colon cancer (CC). Methods: HORG-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX with primary end point the 3 years DFS (3yDFS). Results: In total 1121 patients, 413 with high risk stage and 708 with stage IIICC, were randomized between May 2009 and October 2015. The median follow-up was 67 (38-126) months. There were 79 DFS events (43 in 3M and 38 in 6M arm) in high risk stage II patients leading to 3yDFS rate of 82.7 and 83.4% for 3M and 6M, respectively (HR: 1.05; 95%CI: 0.68-1.63, p = 0.829). Similarly, 214 DFS events (161 in 3M and 153 in 6M arm) has been recorded in stage III patients, leading to a 3yDFS rate of 72.9% in the 3M vs. 74.1% in the 6M (HR = 1.06; 95%CI: 0.81–1.42, p = 0.622). For high risk stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% in the 3M vs.79.3% in the 6M (HR = 1.21; 95%CI: 0.54–2.70 p = 0.641). For high risk stage II patients receiving CAPOX 3-year DFS rate was 85.4% in the 3M vs. 83.8% in the 6M (HR = 0.99; 95%CI: 0.59–1.67 p = 0.968). For stage III CC patients receiving mFOLFOX6, 3-year DFS rate was 71.5% in the 3M vs.77.3% in the 6M (HR = 1.18; 95%CI: 0.74–1.86 p = 0.479). For stage III CC patients receiving CAPOX 3-year DFS rate was 74.5% in the 3M vs. 74.7% in the 6M (HR = 0.99; 95%CI: 0.70–1.44 p = 0.991). Conclusions: The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that 3yDFS is depended on the administered adjuvant regimen, and the choice of regimen and duration should be personalized. Clinical trial information: NCT01308086.

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