Thymidine phosphorylase and dihydropyrimidine dehydrogenase levels in primary colorectal cancer show a relationship to clinical effects of 5'-deoxy-5-fluorouridine as adjuvant chemotherapy

(1) Background: The optimal timing of adjuvant chemotherapy (CT) in gastrointestinal malignancies is still a matter of debate. For colorectal cancer, it is recommended to start post-operative treatment within eight weeks. The objective of this study was to assess the clinical effects of starting adjuvant CT within or after 6–8 weeks post-surgery in colorectal, gastric, and pancreatic cancer. (2) Methods: MEDLINE, EMBASE, and the Cochrane Library were searched in December 2018. Publications comparing the outcomes of patients treated with adjuvant CT administered before (early) or after (delayed) 6–8 weeks post-surgery for colorectal, gastric, and pancreatic cancer were identified. The primary endpoint was overall survival (OS). (3) Results: Out of 8752 publications identified, 34 comparative studies assessing a total of 141,853 patients were included. Meta-analysis indicated a statistically significant increased risk of death with delayed CT (>6–8 weeks post-surgery) in colorectal cancer (hazard ratio (HR) = 1.27, 95% confidence interval (CI) 1.21–1.33; p <0.001). Similarly, for gastric cancer, delaying adjuvant CT was associated with inferior overall survival (HR = 1.2, 95% CI 1.04–1.38; p = 0.01). Conversely, the benefit of earlier CT was not evident in pancreatic cancer (HR = 1, 95% CI 1–1.01; p = 0.37). Conclusions: Starting adjuvant CT within 6–8 weeks post-surgery is associated with a significant survival benefit for colorectal and gastric cancer, but not for pancreatic cancer.

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283 Evaluation of thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA levels in colorectal cancer reveals significant correlations to tumor histopathology and disease-free survival in 5-FU treated patients

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(03)90316-8 ◽

2003 ◽

Vol 1 (5) ◽

pp. S87

Author(s):

S. Lassmann ◽

M. Hennig ◽

R. Rosenberg ◽

J. Nährig ◽

J. Schreglmann ◽

...

Keyword(s):

Colorectal Cancer ◽

Thymidylate Synthase ◽

Thymidine Phosphorylase ◽

Dihydropyrimidine Dehydrogenase ◽

Disease Free Survival ◽

Mrna Levels ◽

Free Survival ◽

Disease Free

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Topoisomerase I protein expression in primary colorectal cancer and recurrences after 5-FU-based adjuvant chemotherapy

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-007-0253-6 ◽

2007 ◽

Vol 133 (12) ◽

pp. 1011-1015 ◽

Cited By ~ 6

Author(s):

P. Gouveris ◽

A. C. Lazaris ◽

T. G. Papathomas ◽

A. Nonni ◽

V. Kyriakou ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Protein Expression ◽

Topoisomerase I ◽

Primary Colorectal Cancer

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Thymidine Phosphorylase Expression Is Associated With Response to Capecitabine Plus Irinotecan in Patients With Metastatic Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.05.2084 ◽

2006 ◽

Vol 24 (25) ◽

pp. 4069-4077 ◽

Cited By ~ 71

Author(s):

Neal J. Meropol ◽

Philip J. Gold ◽

Robert B. Diasio ◽

Michael Andria ◽

Mandeep Dhami ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Odds Ratio ◽

Thymidine Phosphorylase ◽

Dihydropyrimidine Dehydrogenase ◽

Predictive Marker ◽

Clinical Activity ◽

Primary Tumors ◽

Gene And Protein Expression ◽

Biomarker Analysis

Purpose To evaluate the clinical activity and toxicity of capecitabine plus irinotecan as first-line therapy for patients with metastatic colorectal cancer (mCRC), and to describe the association of expression of thymidine phosphorylase (TP), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) with antitumor activity. Patients and Methods Patients with previously untreated mCRC received irinotecan days 1 and 8 intravenously, and capecitabine days 2 to 15 orally in 21-day cycles. Doses were irinotecan 125 mg/m2 and capecitabine 1,000 mg/m2 bid (n = 15; cohort 1), or irinotecan 100 mg/m2 and capecitabine 900 mg/m2 bid (n = 52; cohort 2). Tissues from primary and metastatic sites were assessed for TP, TS, and DPD gene and protein expression. Results An unacceptable level of GI toxicity in the first 15 patients led to a protocol modification in starting doses. The response rate was 45% (30 of 67 patients). Overall survival was associated with TP expression assessed by immunohistochemistry in both primary tumors (P = .045) and metastases (P = .001). Objective tumor response was associated with TP expression in primary tumors (odds ratio, 4.77; 95% CI, 1.25 to 18.18), with a similar trend in metastases (odds ratio, 8.67; 95% CI, 0.95 to 79.1). TP gene expression in primary tumors was also associated with response. Conclusion These data indicate that capecitabine plus irinotecan is an active regimen against mCRC. The biomarker analysis (including metastatic tissue) was feasible in a multicenter setting, and provides preliminary evidence that TP expression may be a predictive marker for response.

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