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Thymidine synthase, thymidine phosphorylase, and excision repair cross-complementation group 1 expression as predictive markers of capecitabine plus cisplatin chemotherapy as first-line treatment for patients with advanced oesophageal squamous cell carcinoma.

Lee S, Park YH, Kim KH, Cho EY, Ahn YC, Kim K, Shim YM, Ahn JS, Park K, Im YH - Br. J. Cancer (2010)

Bottom Line: High expression of TS and TP was associated with a higher RR than was low expression of TS and TP (54.1 vs 40.5%, P=0.022).Strong ERCC1 expression and a low TS score were identified as unfavourable independent risk factors for PFS (HR 10.71, 95% confidence interval (CI) 2.1-54.7, P=0.004 for strong ERCC1 expression; and HR 2.9, 95% CI 1.0-7.9, P=0.044 for low TS score).Strong ERCC1 expression was identified as an unfavourable independent risk factor for OS (HR 3.73, 95% CI 1.39-10.0, P=0.009).

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea.

ABSTRACT

Background: Our purpose was to evaluate thymidine synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementation group 1 (ERCC1) expression as biomarkers for capecitabine and cisplatin (XP) combination chemotherapy in patients with metastatic oesophageal squamous cell cancer.

Method: A total of 113 patients with metastatic oesophageal squamous cell cancer were treated with XP chemotherapy at the Samsung Medical Center between 2003 and 2007, of whom 72 had available clinical data and paraffin blocks for immunohistochemistry of TS, TP, and ERCC1.

Results: The median age of the 72 patients was 62 years. The overall response rate (RR) was 51.4%. The median progression-free survival (PFS) and overall survival (OS) were 4.2 and 12.0 months, respectively. High expression of TS and TP was associated with a higher RR than was low expression of TS and TP (54.1 vs 40.5%, P=0.022). Strong ERCC1 expression and a low TS score were identified as unfavourable independent risk factors for PFS (HR 10.71, 95% confidence interval (CI) 2.1-54.7, P=0.004 for strong ERCC1 expression; and HR 2.9, 95% CI 1.0-7.9, P=0.044 for low TS score). Strong ERCC1 expression was identified as an unfavourable independent risk factor for OS (HR 3.73, 95% CI 1.39-10.0, P=0.009).

Conclusion: These data indicate that expression of TS, TP, and ERCC1 may be predictive markers for response and survival in patients with metastatic oesophageal squamous cell cancer receiving XP chemotherapy.

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Related in: MedlinePlus

Kaplan–Meier curve for PFS and OS of XP in metastatic oesophageal SCCA.
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fig2: Kaplan–Meier curve for PFS and OS of XP in metastatic oesophageal SCCA.

Mentions: The association between TS, TP, and ERCC1, and response to XP, as measured by IHC, is listed in Table 3. A high TS proportion, high TS intensity, and high TS score predicted a response (TS<25% vs TS ⩾25%, RR 40.5 vs 59.5%, P=0.009; TS intensity 0–1 vs 2–3, RR 45.9 vs 54.1, P=0.030; TS score ⩽6 vs TS score>6, RR 40.5 vs 59.5%, P=0.005). High expression of TS and TP was also significantly correlated with treatment response to the XP regimen (high TS and TP vs low TS and TP, RR 54.1 vs 45.9%, P=0.022). High TS and TP expression with low ERCC1 expression (0–2 vs 3) showed a significantly better response compared with other levels of expression (high TS and TP and low ERCC1 vs other levels of expression, RR 63.2 vs 36.8%, P=0.016; Table 3, Figures 2, 3 and 4). In addition, quantitative analysis, as well as TS and TP extents, showed significant correlation with responses (RR 3.77, P<0.0001 for TS extent (%); RR 4.12, P=0.045 for TP extent by ANOVA test, Table 3).


Thymidine synthase, thymidine phosphorylase, and excision repair cross-complementation group 1 expression as predictive markers of capecitabine plus cisplatin chemotherapy as first-line treatment for patients with advanced oesophageal squamous cell carcinoma.

Lee S, Park YH, Kim KH, Cho EY, Ahn YC, Kim K, Shim YM, Ahn JS, Park K, Im YH - Br. J. Cancer (2010)

Kaplan–Meier curve for PFS and OS of XP in metastatic oesophageal SCCA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2966625&req=5

fig2: Kaplan–Meier curve for PFS and OS of XP in metastatic oesophageal SCCA.
Mentions: The association between TS, TP, and ERCC1, and response to XP, as measured by IHC, is listed in Table 3. A high TS proportion, high TS intensity, and high TS score predicted a response (TS<25% vs TS ⩾25%, RR 40.5 vs 59.5%, P=0.009; TS intensity 0–1 vs 2–3, RR 45.9 vs 54.1, P=0.030; TS score ⩽6 vs TS score>6, RR 40.5 vs 59.5%, P=0.005). High expression of TS and TP was also significantly correlated with treatment response to the XP regimen (high TS and TP vs low TS and TP, RR 54.1 vs 45.9%, P=0.022). High TS and TP expression with low ERCC1 expression (0–2 vs 3) showed a significantly better response compared with other levels of expression (high TS and TP and low ERCC1 vs other levels of expression, RR 63.2 vs 36.8%, P=0.016; Table 3, Figures 2, 3 and 4). In addition, quantitative analysis, as well as TS and TP extents, showed significant correlation with responses (RR 3.77, P<0.0001 for TS extent (%); RR 4.12, P=0.045 for TP extent by ANOVA test, Table 3).

Bottom Line: High expression of TS and TP was associated with a higher RR than was low expression of TS and TP (54.1 vs 40.5%, P=0.022).Strong ERCC1 expression and a low TS score were identified as unfavourable independent risk factors for PFS (HR 10.71, 95% confidence interval (CI) 2.1-54.7, P=0.004 for strong ERCC1 expression; and HR 2.9, 95% CI 1.0-7.9, P=0.044 for low TS score).Strong ERCC1 expression was identified as an unfavourable independent risk factor for OS (HR 3.73, 95% CI 1.39-10.0, P=0.009).

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea.

ABSTRACT

Background: Our purpose was to evaluate thymidine synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementation group 1 (ERCC1) expression as biomarkers for capecitabine and cisplatin (XP) combination chemotherapy in patients with metastatic oesophageal squamous cell cancer.

Method: A total of 113 patients with metastatic oesophageal squamous cell cancer were treated with XP chemotherapy at the Samsung Medical Center between 2003 and 2007, of whom 72 had available clinical data and paraffin blocks for immunohistochemistry of TS, TP, and ERCC1.

Results: The median age of the 72 patients was 62 years. The overall response rate (RR) was 51.4%. The median progression-free survival (PFS) and overall survival (OS) were 4.2 and 12.0 months, respectively. High expression of TS and TP was associated with a higher RR than was low expression of TS and TP (54.1 vs 40.5%, P=0.022). Strong ERCC1 expression and a low TS score were identified as unfavourable independent risk factors for PFS (HR 10.71, 95% confidence interval (CI) 2.1-54.7, P=0.004 for strong ERCC1 expression; and HR 2.9, 95% CI 1.0-7.9, P=0.044 for low TS score). Strong ERCC1 expression was identified as an unfavourable independent risk factor for OS (HR 3.73, 95% CI 1.39-10.0, P=0.009).

Conclusion: These data indicate that expression of TS, TP, and ERCC1 may be predictive markers for response and survival in patients with metastatic oesophageal squamous cell cancer receiving XP chemotherapy.

Show MeSH
Related in: MedlinePlus