A prospective pharmacogenetic study of thymidylate synthase (TS) polymorphisms in high risk stage II or stage III colon cancer patients treated with 5-fluorouracil (5-FU) and leucovorin (LV)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13018-13018
Author(s):  
K. E. Mulder ◽  
C. A. Butts ◽  
A. Scarfe ◽  
H. Au ◽  
S. Koski ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Binding Sites ◽  
Retrospective Studies ◽  
Stage Ii ◽  
Stage Iii ◽  
Pharmacogenetic Study ◽  
Stage Iii Colon Cancer ◽  
E Box

13018 Background: Retrospective studies suggest TS polymorphisms predict toxicity from TS inhibitors as well as therapeutic response. The TS promoter has a variable number of tandem repeats (VNTR) polymorphism containing putative E-box binding sites that bind upstream stimulatory factor (USF) -1 and -2. One E-box binding site exists in TSER*2 and 2 binding sites exist in TSER*3. A single nucleotide polymorphism (SNP) at position 12 (G→C) in TSER*3’s 2nd repeat abolishes binding of USF-1/2. Combined effects of VNTR and SNP means individuals may have 2, 3 or 4 enhancer regions. We hypothesized that decreased enhancer numbers predicts for patients at risk for grade ≥3 mucositis, diarrhea, neutropenia, and overall toxicity and performed a prospective pharmacogenetic study of TS polymorphisms in adjuvant colon cancer patients treated with 5-FU/LV. Methods: High risk Stage II or Stage III colon cancer patients treated with 5FU/LV (425 mg/m2/ 20 mg/m2) daily for 5 days every 4 weeks had blood drawn for genotyping prior to starting therapy. Patients were assessed for toxicity using NCI CTC 2.0 in cycle 1. Three year disease-free survival will also be assessed. Results: 103 patients were enrolled and genotyped with 95 evaluable for toxicity. Patient characteristics: median age 61yrs (36–79): M 52%/F 48%; Stage III 77%, Stage II 23%. Frequency of genotypes containing 2 enhancers (TSER*2/ TSER*2, TSER*2 / TSER*3C, TSER*3C/ TSER*3C), 3 enhancers (TSER*2/ TSER*3G, TSER*3C/ TSER*3G) and 4 enhancers (TSER*3G/ TSER*3G) was 0.64, 0.31, and 0.05 respectively. No significant difference was seen in overall toxicity, mucositis, diarrhea and neutropenia based on TS polymorphism genotypes. Frequency of recurrence in 2 enhancer patients was 13% versus 26% in 3/4 enhancer patients but this did not reach statistical significance (p = 0.16). Conclusions: This prospective study does not confirm previously published retrospective studies suggesting that TS VNTR and SNP predict toxicity from TS inhibitors in patients treated with 5-fluorouracil for colon cancer. There is a trend for prediction of recurrence which requires further follow-up. No significant financial relationships to disclose.

scholarly journals Review: Combination therapy in high-risk stage II or stage III colon cancer: current practice and future prospects

2010 ◽  
Vol 2 (4) ◽  
pp. 261-272 ◽  
Author(s):  
Diogo Assed Bastos ◽  
Suilane Coelho Ribeiro ◽  
Daniela de Freitas ◽  
Paulo M. Hoff
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Combination Therapy ◽  
Current Practice ◽  
Stage Ii ◽  
Stage Iii ◽  
Future Prospects ◽  
Stage Iii Colon Cancer

scholarly journals Predictive potential of tumour-stroma ratio on benefit from adjuvant bevacizumab in high-risk stage II and stage III colon cancer

2017 ◽  
Vol 28 ◽  
pp. v168-v169
Author(s):  
S. Zunder ◽  
G. van Pelt ◽  
H. Gelderblom ◽  
R. Tollenaar ◽  
C. Mancao ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Tumour Stroma ◽  
Stage Iii Colon Cancer

Abstract CT263: Post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients: The PEGASUS trial

2020 ◽  
Author(s):  
Elena Elez ◽  
Filippo Pietrantonio ◽  
Andrea Sartore-Bianchi ◽  
Clara Montagut ◽  
Andres Cervantes ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Ii Colon Cancer

scholarly journals The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients

2010 ◽  
Vol 21 (12) ◽  
pp. 2396-2402 ◽  
Author(s):  
A. Fariña-Sarasqueta ◽  
G. van Lijnschoten ◽  
E. Moerland ◽  
G.-J. Creemers ◽  
V.E.P.P. Lemmens ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Braf V600e Mutation ◽  
Independent Prognostic Factor ◽  
Stage Ii ◽  
Braf V600e ◽  
Stage Iii ◽  
Stage Iii Colon Cancer

VEGF and VEGF receptor-2 (VEGFR2) gene polymorphisms predict tumor recurrence in stage II and III colon cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4004-4004 ◽  
Author(s):  
G. Lurje ◽  
A. M. Schultheis ◽  
A. E. Hendifar ◽  
S. Ashouri ◽  
W. Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Tumor Recurrence ◽  
Stage Ii ◽  
Stage Iii ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Vegf Receptor ◽  
Stage Iii Colon Cancer ◽  
Increased Risk

4004 Background: Despite recent advances in the treatment of metastatic colorectal cancer, tailoring adjuvant treatment of stage II and III colon cancer patients remains controversial. Identifying a reliable panel of prognostic and predictive markers for tumor recurrence is critical in selecting an individualized and tailored chemotherapy. Tumor angiogenesis plays an important role in tumor development, progression and metastasis. In this retrospective study, we tested whether a specific pattern of 40 functionally significant polymorphisms in 37 genes involved in angiogenesis and tumor microenvironment will predict the risk of tumor recurrence in stage II and III colon cancer patients treated with adjuvant chemotherapy. Methods: Between 1999 and 2006 blood specimens from 140 patients (69 females and 71 males with a median age of 59 years; range=28–86) were obtained at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC). Sixty-three patients had stage II and 77 had stage III colon cancer. The median follow-up was 5.4 years (range=2.0–16.8). 51 of 140 patients (36.4%) developed tumor recurrence with a 5-year probability of 0.28 ± 0.06 for stage II and 0.40 ± 0.06 for stage III colon cancer patients. Genomic DNA was extracted from peripheral blood and genotypes were determined using PCR based RFLP. Results: Polymorphisms in VEGF (C936T; p=0.009, log-rank) and VEGFR2 (+4422 AC- repeat; p=0.04, log-rank and +1416 T/A; p=0.0009, log-rank) were associated with risk of tumor recurrence in stage III colon cancer patients (n=77). VEGFR2 AC-repeat polymorphisms were additionally associated with risk of recurrence in Stage II colon cancer patients (n=63, p=0.02, log-rank). Conclusion: VEGF C936T and VEGFR2 (+4422 AC-repeat and +1416 T/A) polymorphisms may help to identify Stage II and III colon cancer patients who are at increased risk for developing tumor recurrence. Angiogenesis seems to play a crucial role in tumor recurrence, thus targeting VEGF and VEGFR2 may be of clinical benefit for stage II and stage III colon cancer patients. Large prospective trials are needed to validate these preliminary data. No significant financial relationships to disclose.

The effect of gaps in chemotherapy on survival in patients with high-risk stage II and stage III colon cancer.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 180-180
Author(s):  
Yvonne Sada ◽  
Zhigang Duan ◽  
Hashem El-Serag ◽  
Jessica Davila
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Factors ◽  
Stage Iii Colon Cancer ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Multivariable Regression ◽  
The Impact

180 Background: Current guidelines recommend six months of chemotherapy (CT) for stage III colon cancer and consideration for high-risk stage II colon cancer. No previous studies have examined the impact of CT gaps on survival. This retrospective study examines determinants of CT gaps and the effect of gaps on survival. Methods: Using national Surveillance, Epidemiology, and End Results registry-Medicare linked data, high-risk stage II and stage III colon cancer patients diagnosed between 2000-2007 who received surgery and CT were identified. CT duration and gaps were calculated. CT gap was defined as 30 to 90 days between two CT claims. Data on demographics, clinical factors (comorbidity, tumor grade), and treatment factors (time to CT initiation, toxicity, hospitalization) were collected. Multivariable regression was used to examine factors associated with gaps. Cox proportional hazards analysis examined the effect of gaps on risk of mortality. Results: 7,371 patients were identified. Median age was 75 (IQR: 71-79); 47% were male. Among all patients, 1,803 (24%) had a gap. 2,674 patients (36%) received 5 to 7 months of CT, of which 469 (18%) had a gap. Multivariable regression analysis showed that patients who were black (OR 1.3, 95% CI: 1.1-1.7), stage III (1.2, 1.0-1.3), had toxicity (1.3, 1.1-1.4), or had 3 to 4 months of CT (vs. 5-7 months, 2.6, 2.3-3.0) were more likely to have a gap, while patients with a more recent diagnosis in 2007(vs. 2000, 0.6, 0.5-0.8) were less likely to have a gap. 3-year cancer-specific survival was the same in all patients with CT gaps compared with no gaps (80%, 95% CI: 78%-82% vs. 81%, 95% CI: 80%-82%). Cox proportional hazard models showed that patients with gaps did not have increased risk of mortality (HR 0.99, 0.89-1.1) adjusting for patient and clinical factors. Among those who received 5 to 7 months of CT, 3-year survival was 8% lower in patients with gaps compared to those with no gaps (80%, 95% CI: 75%-83% vs. 88%, 95% CI: 87%-90%). Conclusions: Nearly 25% of high-risk stage II and III patients who received CT had a gap. CT gaps were associated with worse survival in patients who received 5 to 7 months of CT. Interventions to improve CT toxicity management and reduce gaps are needed to maximize the benefit of CT.

scholarly journals Impact of relative dose intensity of FOLFOX adjuvant chemotherapy on risk of death among stage III colon cancer patients

2020 ◽  
Author(s):  
Meijiao Zhou ◽  
Trevor D. Thompson ◽  
Hui-Yi Lin ◽  
Vivien W. Chen ◽  
Jordan J. Karlitz ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Dose Intensity ◽  
Low Risk ◽  
Relative Dose Intensity ◽  
Stage Iii ◽  
Risk Of Death ◽  
Stage Iii Colon Cancer ◽  
Risk Patients

Abstract Background Clinical trials have indicated high-risk (T4 and/or N2) and low-risk (T1-T3 and N1) stage III colon cancer patients might need different doses of FOLFOX to reserve a similar survival probability. Observational studies have investigated the effect of relative dose intensity (RDI) of FOLFOX on cancer survival for patients with stage III colon cancer, but nonetheless, the studies focused on very specific populations, and none performed stratified analysis by risk profiles. This study aims to identify the optimal RDI of FOLFOX administered for high-risk and low-risk stage III colon cancer patients.Methods Data on 407 eligible patients, diagnosed with stage III colon cancer in 2011 who received FOLFOX, were collected by the eight population-based cancer registries for a CDC National Program of Cancer Registries (NPCR) project focused on Comparative Effectiveness Research. We employed Kaplan-Meier method, cumulative incidence function (CIF), Multivariable Cox model and Fine-Gray competing risks model to explore Optimal Relative Dose Intensity (RDI) defined as the lowest RDI administered without significant differences in either overall or cause-specific death.Results Among the 168 high-risk patients, the optimal RDI cut-off point was 70% where there was no statistically significant difference in overall mortality (HR=1.87; 95% CI: 0.84-4.19) and cause-specific mortality (HR=1.72; 95% CI: 0.61-4.85) when RDI<70% vs. RDI≥70%, adjusting for sociodemographic and clinical covariates. When the RDI cut-off was lower than the optimal one (<55% vs. ≥55%, <60% vs. ≥60%, or <65% vs. ≥65%), the overall and cause-specific mortalities were significantly statistically different between the two groups of each comparison. Among the 239 low-risk patients, none of the evaluated cut-offs were associated with statistically significant differences in overall and cause-specific mortalities between comparison groups. The lowest RDI we assessed was 45%, HR=0.79; 95% CI: 0.23-2.67 for the overall mortality and HR=0.49; 95% CI: 0.05-4.84 for the cause-specific mortality, when RDI<45% vs. RDI≥45%.Conclusions To best utilize health care resources while maintaining efficacy, RDI can be maintained at a minimum of 70% in high-risk stage III colon cancer patients. For low-risk patients, we found that RDI as low as 45% did not impact risk of death.

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