ecancermedicalscience

Short Communication

Association of serum cyclooxygenase-2 levels with hand-foot syndrome in patients receiving capecitabine: an exploratory analysis of D-TORCH study

15 Aug 2025
Ghazal Tansir, Akhil Santhosh, Akash Kumar, Hemavathi Baskarane, Mohit Kumar Divakar, Vishakha Hooda, Arundhati J R Dev, Chandra Prakash Prasad, Ishaan Gupta, Saran Kumar, Pranay Tanwar, Atul Sharma, Sameer Bakhshi, Atul Batra

Background: The D-TORCH trial demonstrated superiority of 1% topical diclofenac over placebo in preventing capecitabine-induced hand-foot syndrome (HFS). We conducted an exploratory analysis of this study to assess the relationship between HFS and serum levels of the inflammatory marker, cyclooxygenase-2 (COX-2).

Methods: Serum COX-2 levels were measured in patients in the D-TORCH study's experimental and placebo arms at baseline and 12 weeks of capecitabine-based therapy or at the development of HFS (whichever occurred earlier) and in 20 age-matched healthy controls using a human COX-2 ELISA kit (E-EL-H5574).

Results: 233 (88.5%) patients of the D-TORCH cohort (n = 263) underwent serial COX-2 analysis. The population was female predominant (n = 165, 70.8) with a median age of 47 years (range: 19–73), including breast (n = 130, 55.8%) and gastrointestinal cancers (n = 103, 44.2%). 31 (13.3%) patients developed any-grade HFS, with 25 (10.7%) having grade 2 or worse HFS. Mean serum COX-2 levels at baseline and 12 weeks did not show a statistically significant difference (mean + standard deviation, 3.41 + 2.15 ng/ml versus 3.35 + 2.40 ng/ml, p = 0.69); however, baseline levels in patients were significantly higher than healthy controls (p < 0.001). No statistically significant difference was found between serial COX-2 levels by gender, use of topical diclofenac, type of malignancy or severity of HFS.

Conclusion: Serum COX-2 levels did not show a significant change with capecitabine-based therapy, regardless of the use of topical diclofenac possibly reflecting the predominant stromal production of the enzyme. This finding highlights the need to assess HFS-affected tissues for local COX-2 immuno-expression along with further blood-based biomarkers.

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