Single-center phase 3 trial of topical diclofenac versus placebo for prevention of capecitabine-associated hand-foot syndrome

Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting COX-2 that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib limit routine prescription. The phase 3 D-TORCH trial, at the All India Institute of Medical Science (Delhi), evaluated topical diclofenac versus placebo for the prevention of capecitabine-associated HFS. Patients with breast or GI cancer who were planned to receive capecitabine-based treatment were randomized 1:1 to topical diclofenac gel or placebo gel. Grade 2 or 3 HFS (primary end point) was observed in 3.8% of patients in the diclofenac group versus 15.0% of patients in the placebo group (p=0.003). Grade 1-3 HFS was seen in 6.1% versus 18.1%, and capecitabine dose reductions because of HFS in 3.8% versus 13.5%. The authors conclude that topical diclofenac reduces the risk of HFS in patients receiving capecitabine.