Determination of thymidine phosphorylase expression level facilitates recurrence risk stratification in stage II/III colorectal cancer following adjuvant chemotherapy with oral fluoropyrimidines

Colorectal cancer alone accounts for around 200,000 deaths in Europe and represents a significant health problem. Although about fifty percent of patients are cured by surgery alone, the other half will eventually die due to metastatic disease, which includes approximately 25% of patients who have evidence of metastases at the time of diagnosis. Surgical resection of the primary tumor and regional lymph nodes is the only curative therapy for colorectal cancer. However, adjuvant chemotherapy in stage III for colon cancer following curative resection has been shown to reduce the risk of recurrence by 19-40% and of death by 16-33%. Today, 5-fluoroUracil and Leucovorin given for six months may represent the best adjuvant treatment available The contribution of levamisole to adjuvant treatment seems to be marginal, if any. The benefit of adjuvant chemotherapy for the patients with Dukes B colon cancer is less clear. A meta-analysis of 1,381 patients with advanced colorectal cancer showed a significant increase in response rate with the bolus 5-fluoroUracil and Leucovorin versus 5-fluoroUracil alone but no significant difference in median survival. Continuous infusion allows higher doses of 5-FU than rapid bolus infusion and improves response rate survival and time to progression. Oral fluoropyrimidines (capecitabine and Uracil/Tegafur [UFT]) are as active as intravenous fluoropyrimidines. Compared to intravenous 5FU, oral fluoropyrimidines have safety advantages clinical benefits, and are more convenient for patients. Phase III randomized clinical trials in patients with metastatic colorectal cancer demonstrate the significant superiority of combining irinotecan with 5-fluoroUracil and Leucovorin or oxaliplatin with 5-fluoroUracil and Leucovorin over the same 5-fluoroUracil and Leucovorin alone. Several phase II studies have shown that the combination of the oral fluoropyrimidines plus irinotecan or oxaliplatin is very active in metastatic colorectal cancer. Trials with agents acting on novel targets in colorectal cancer are progressing rapidly, including doxifluridine, new inhibitors of thymidylate synthase (ZD9331), oral camptothecins (Rubitecan), multitarget antifolate antimetabolite (Premetrexet), inhibitors of epidermal growth factor receptor (Cetuximab), COX-2 inhibitors (celecoxib) and farnesyltransferaze inhibitors (Zarnestra). However, a few randomized trials failed to show a survival advantage compared with placebo in patients with advanced refractory colorectal cancer.

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A biological perspective on the selection of stage II colorectal cancer patients for adjuvant chemotherapy

Annals of Oncology ◽

10.1093/annonc/mdf245 ◽

2002 ◽

Vol 13 (9) ◽

pp. 1510 ◽

Cited By ~ 1

Author(s):

B. Iacopetta

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Stage Ii ◽

Biological Perspective ◽

Stage Ii Colorectal Cancer ◽

Colorectal Cancer Patients ◽

Selection Of

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Prognostic impact of interhospital variation in adjuvant chemotherapy for patients with Stage II/III colorectal cancer: a nationwide study

Colorectal Disease ◽

10.1111/codi.14260 ◽

2018 ◽

Vol 20 (7) ◽

pp. O162-O172 ◽

Cited By ~ 1

Author(s):

K. Arakawa ◽

K. Kawai ◽

T. Tanaka ◽

K. Hata ◽

K. Sugihara ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Stage Ii ◽

Prognostic Impact ◽

Nationwide Study

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Clinical and Socioeconomic Factors that Predict Non-completion of Adjuvant Chemotherapy for Colorectal Cancer in a Rural Cancer Center

The American Surgeon ◽

10.1177/00031348211054708 ◽

2022 ◽

pp. 000313482110547

Author(s):

Chelsea Knotts ◽

Alexandra Van Horn ◽

Krysta Orminski ◽

Stephanie Thompson ◽

Jacob Minor ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Socioeconomic Factors ◽

Cancer Patients ◽

Private Insurance ◽

Stage Ii ◽

Stage Iii ◽

Insurance Status ◽

Complete Treatment ◽

Colorectal Cancer Patients

Background Previous literature demonstrates correlations between comorbidities and failure to complete adjuvant chemotherapy. Frailty and socioeconomic disparities have also been implicated in affecting cancer treatment outcomes. This study examines the effect of demographics, comorbidities, frailty, and socioeconomic status on chemotherapy completion rates in colorectal cancer patients. Methods This was an observational case-control study using retrospective data from Stage II and III colorectal cancer patients offered chemotherapy between January 01, 2013 and January 01, 2018. Data was obtained using the cancer registry, supplemented with chart review. Patients were divided based on treatment completion and compared with respect to comorbidities, age, Eastern Cooperative Oncology Group (ECOG) score, and insurance status using univariate and multivariate analyses. Results 228 patients were identified: 53 Stage II and 175 Stage III. Of these, 24.5% of Stage II and 30.3% of Stage III patients did not complete chemotherapy. Neither ECOG status nor any comorbidity predicted failure to complete treatment. Those failing to complete chemotherapy were older (64.4 vs 60.8 years, P = .043). Additionally, those with public assistance or self-pay were less likely to complete chemotherapy than those with private insurance ( P = .049). Both factors (older age/insurance status) remained significant on multivariate analysis (increasing age at diagnosis: OR 1.03, P =.034; public insurance: OR 1.84, P = .07; and self-pay status: OR 4.49, P = .03). Conclusions No comorbidity was associated with failure to complete therapy, nor was frailty, as assessed by ECOG score. Though frailty was not significant, increasing age was, possibly reflecting negative attitudes toward chemotherapy in older populations. Insurance status also predicted failure to complete treatment, suggesting disparities in access to treatment, affected by socioeconomic factors.

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