Genetic polymorphisms and ethnic difference in outcome of adjuvant FOLFOX chemotherapy in Korean patients with colon cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 623-623
Author(s):  
Kyung-Hun Lee ◽  
Hye Jung Chang ◽  
Sae-Won Han ◽  
Do-Youn Oh ◽  
Seock-Ah Im ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Ethnic Difference ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Toxicity Profile ◽  
Free Survival ◽  
Korean Patients ◽  
Folfox Chemotherapy ◽  
Disease Free

623 Background: Ethnic diversity of genetic polymorphism can result in individual differences in the efficacy and toxicity of cancer chemotherapy. Methods: A total of 292 Korean patients (183 men and 109 women) from six hospitals in Korea were prospectively enrolled. Patients had resected stage III or high-risk stage II colon cancer and were treated with 12 cycles of adjuvant oxaliplatin plus leucovorin plus 5-fluorouracil (FOLFOX) chemotherapy. 20 germline polymorphisms in 10 genes (TS, MTHFR, ERCC1, XPD, XRCC1, ABCC2, AGXT, GSTP1, GSTT1 and GSTM1) were analyzed from peripheral blood. TS genotype in 5’UTR was classified as ‘high’ (2R/3G, 3C/3G, and 3G/3G) or ‘low’ (2R/2R, 2R/3C, and 3C/3C). Results: Most patients (86.3%) received 12 complete cycles of FOLFOX chemotherapy. In contrast to previous studies in Caucasians, neutropenia (grade 3–4, 60.5%) was frequently observed in our Korean patients, whereas only 16.4% experienced grade 2 or more sensory neuropathy. Neutropenia was more frequent in MTHFR 677TT [adjusted odds ratio (OR) 2.32, 95% confidence interval (CI) 1.19–4.55] and ERCC1 19007TT (adjusted OR 4.58, 95% CI 1.20–17.40) genotypes. Patients harboring XRCC1 23885GG had lower risk of neuropathy (adjusted hazard ratio 0.56, 95% CI 0.32-0.99) and longer time to the onset of grade 2-4 neuropathy. MTHFR 677TT and XRCC1 23885GG genotype was also more prevalent in Koreans compared to Caucasians, and the difference of genotypic frequency could partly explain the ethnically different toxicity profile. After median 49.4 months of follow-up, there were 58 (19.9%) relapses and 19 (6.5%) deaths. TS ‘low’ genotype [adjusted hazard ratio (OR) 1.83, 95% CI 1.003–3.34] was significantly related to shorter disease-free survival. Overall survival was not significantly different according to the polymorphisms. Conclusions: Polymorphisms in MTHFR, XRCC1 and TS are related to toxicities and disease-free survival in patients with colon cancer. These polymorphisms may explain the ethnic difference in toxicity profile following adjuvant FOLFOX chemotherapy.

Defective Mismatch Repair Status as a Prognostic Biomarker of Disease-Free Survival in Stage III Colon Cancer Patients Treated with Adjuvant FOLFOX Chemotherapy

2011 ◽  
Vol 17 (23) ◽  
pp. 7470-7478 ◽  
Author(s):  
Aziz Zaanan ◽  
Jean-François Fléjou ◽  
Jean-François Emile ◽  
Guetz Gaëtan Des ◽  
Peggy Cuilliere-Dartigues ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Prognostic Biomarker ◽  
Disease Free Survival ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Mismatch Repair Status ◽  
Folfox Chemotherapy ◽  
Disease Free ◽  
Defective Mismatch Repair

Mucinous histology to predict disease-free survival in microsatellite stable stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14084-e14084
Author(s):  
Joong Bae Ahn ◽  
Se Hyun Kim ◽  
Sang Joon Shin ◽  
Kang Young Lee ◽  
Tae IL Kim ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Poor Prognostic Factor ◽  
Free Survival ◽  
Mucinous Histology ◽  
Stage Iii Colon Cancer ◽  
Folfox Chemotherapy ◽  
Disease Free ◽  
Stable Stage

e14084 Background: The prognostic role of mucinous histology of the colon cancer has been studied for decades and remained controversial. The aim of this retrospective study was to investigate whether mucinous adenocarcinoma (MA) is associated with a worse prognosis than that of non-mucinous adenocarcinoma (NMA) in patients with stage III colon cancer. Methods: This study enrolled unselected 402 patients with stage III colorectal cancer treated with adjuvant FOLFOX after curative resection (R0). Clinicopathological information was retrospectively reviewed. Tumors were analyzed for microsatellite instability (MSI) by polymerase chain reaction (PCR) to determine MSI-high (MSI-H) or microsatellite stable (MSS). Kaplan-Meier method, log-rank test, and Cox proportional hazards regression models were used. Results: Among 402 patients, 42 patients (10.4%) were MA and 26 patients (6.5%) were MSI-H. Compared with MSS tumors, MSI-H tumors was associated with a higher rate of MA (26.9% vs 9.3%, P=0.005). In MSS tumors (n=376), 3-year disease-free survival (DFS) rate was 79% and 55% in NMA and MA, respectively (log rank, P=0.014). In MSI-H tumors (n=26), no statistically significant difference of DFS between MA and NMA was found. In multivariate analysis, MA remained an independent significant poor prognostic factor for DFS (HR=1.9; 95% CI, 1.003-3.717; P=0.049) in MSS patients. Conclusions: Mucinous histology is an independent poor prognostic factor for DFS in patients with microsatellite stable stage III colon cancer after adjuvant FOLFOX chemotherapy. [Table: see text]

Clinical impact of microsatellite instability in patients with stage II and III gastric cancer: Results from the CLASSIC trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4022-4022 ◽  
Author(s):  
Yoon Young Choi ◽  
Hyunki Kim ◽  
Han-Kwang Yang ◽  
Woo Ho Kim ◽  
Young Woo Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Confidence Interval ◽  
Microsatellite Instability ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Stage Ii ◽  
Free Survival ◽  
Disease Free

4022 Background: The clinical implications of microsatellite instability (MSI) in gastric cancer are unclear. We investigated the usefulness of MSI status as a predictor of prognosis and responsiveness to adjuvant chemotherapy in patients with stage II and III gastric cancer. Methods: Tumor specimens and clinical information were collected from patients enrolled in the CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. Five mononucleotide markers were used to assess tumor MSI status. Results: Of 592 specimens, 36 (6.1%) were MSI-high (MSI-H), whereas others were MSI-low or microsatellite-stable (MSS). Among 286 patients not treated with adjuvant therapy, those with MSI-H tumors had a better 5-year disease-free survival rate than did those with MSI-low/MSS tumors (hazard ratio adjusted by age, sex, tumor grade, disease stage, tumor location: 0.244 [95% confidence interval, 0.069–0.867]; p = 0.0292). Among 306 patients who received adjuvant chemotherapy, MSI-H status did not correlate with better disease-free survival (adjusted hazard ratio: 0.561 [95% confidence interval, 0.190–1.654]; p = 0.2946). Benefits from adjuvant chemotherapy differed by MSI status; although adjuvant chemotherapy improved disease-free survival among patients with MSI-low/MSS (adjusted hazard ratio: 0.634 [95% confidence interval, 0.485–0.828]; p = 0.0008), no benefit was observed in the MSI-H group (adjusted hazard ratio: 1.877 [95% confidence interval, 0.284–12.390]; p = 0.5130). Conclusions: Among patients with stage II and III gastric cancer, a MSI-H status correlated with a favorable prognosis, and adjuvant chemotherapy benefited those with MSI-L/MSS tumors but not those with MSI-H tumors.

Effect of a Shortened Duration of FOLFOX Chemotherapy on the Survival Rate of Patients with Stage II and III Colon Cancer

Chemotherapy ◽  
2017 ◽  
Vol 63 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Woong Bae Ji ◽  
Kwang Dae Hong ◽  
Jung-Sik Kim ◽  
Sung-Yup Joung ◽  
Jun Won Um ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Peripheral Neuropathy ◽  
Large Scale ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Significant Difference ◽  
Folfox Chemotherapy ◽  
Disease Free

Background: FOLFOX chemotherapy is widely used as an adjuvant treatment for advanced colon cancer. The duration of adjuvant chemotherapy is usually set to 6 months, which is based on a former study of 5-fluorouracil/leucovorin chemotherapy. However, the FOLFOX regimen is known to have complications, such as peripheral neuropathy. The aim of this study was to compare the survival rates and complications experienced by patients receiving either 4 or 6 months of FOLFOX chemotherapy. Methods: Retrospective data analysis was performed for stage II and III patients who underwent radical resection of colon cancer. We compared the 5-year survival rates and the occurrence of complications in patients who completed only 8 cycles of FOLFOX chemotherapy with patients who completed 12 cycles of chemotherapy. Results: Among 188 patients who underwent adjuvant FOLFOX chemotherapy for stage II or III colon cancer, 83 (44.1%) completed 6 months of FOLFOX chemotherapy and 64 (34.0%) patients discontinued after 4 months of chemotherapy. The 5-year overall survival and disease-free survival rates did not show a significant difference. Patients in the 6-month group had peripheral neuropathy more frequently (p = 0.028). Conclusions: Five-year overall and disease-free survival were not significantly different between the 2 groups. Large-scale prospective studies are necessary for the analysis of complications and survival rates.

Radiomic Signature-Based Nomogram to Predict Disease-Free Survival in Stage II and III Colon Cancer

2019 ◽  
Author(s):  
Xun Yao ◽  
Caixia Sun ◽  
Fei Xiong ◽  
Xinyu Zhang ◽  
Chao Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Disease Free

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.

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

scholarly journals A Bar Code of Selected Gene Copy Number Alterations is Associated with Disease-Free Survival in Stage Ii-Iii Microsatellite Stable (Mss) Colon Cancer

2014 ◽  
Vol 25 ◽  
pp. iv193
Author(s):  
F. Di Fiore ◽  
L. Armengol-Debeir ◽  
F. Blanchard ◽  
C. Chapusot ◽  
B. Tournier ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Gene Copy ◽  
Copy Number Alterations ◽  
Free Survival ◽  
Bar Code ◽  
Disease Free
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