Topical diclofenac prevents HFS in capecitabine-treated cancer patients

Patients with breast or gastrointestinal (GI) cancer who are being treated with capecitabine monotherapy may benefit from using topical diclofenac gel to prevent or reduce the incidence of hand-foot syndrome (HFS), a common side effect of some chemotherapy drugs, reports a recent study presented at ESMO 2023.

In addition, treatment with topical diclofenac has resulted in less frequent reductions in capecitabine dose, according to the investigators, led by Akhil Santhosh from the Department of Medical Oncology, All India Institute of Medical Science, New Delhi, India.

“This is the first study which convincingly established the role of a topical COX inhibitor for HFS prevention,” the investigators said. “Moving forward, we feel this should be the new standard of care and use of topical diclofenac should be regularized in medical oncology outpatient departments.”

Santhosh and colleagues conducted an exploratory subgroup analysis of the D-ToRCH* phase III trial to compare the incidence of grade ≥2 HFS in diclofenac and placebo arms. They also assessed the incidence of any-grade HFS, capecitabine dose reduction due to HFS, and self-reported adherence with application.

The D-ToRCH trial included 264 patients with breast or GI cancer who were about to receive capecitabine to apply either topical diclofenac 1% or placebo gel. A computer-generated random numbers sequence was used to perform stratified (ie, male or female; capecitabine monotherapy or combination therapy), permuted variable size block randomization.

Of the trial participants, 108 received capecitabine monotherapy (56 in the diclofenac arm and 52 in the placebo arm). Baseline characteristics were similar between the two cohorts. Patients had a median age of 47 years, and most of them were female (n=101, 93.5 percent). [ESMO 2023, abstract 2076P]

Furthermore, 67 patients (62 percent) had an ECOG performance status of 0 or 1. Of the participants, 95 (87.9 percent) had breast cancer and 13 GI cancer. Sixty-three patients (58.9 percent) had stage 3 disease, 41 (38.3 percent) had stage 4, and only three (2.8 percent) had stage 2 cancer.

A total of 12 patients developed grade 2 or higher HFS, of whom two were treated with diclofenac and 10 with placebo (3.6 percent vs 19.2 percent; p=0.01). Any-grade HFS occurred in three patients in the diclofenac arm and 12 patients in the placebo arm (5.4 percent vs 23 percent; p=0.008).

Notably, patients treated with diclofenac were less likely to undergo dose reductions of capecitabine relative to those on placebo (3.6 percent vs 19.2 percent; p=0.01). Adherence to topical treatment was also higher in the diclofenac arm than in the placebo arm (93.2 percent vs 82.2 percent; p=0.04).

“Topical diclofenac gel significantly reduced the incidence of all grades of HFS in breast and GI cancer patients receiving capecitabine monotherapy,” the investigators said. “Applying topical diclofenac led to less frequent capecitabine dose reductions.”

HFS development, a dose-limiting side effect of capecitabine, is caused by cyclo-oxygenase-2 (COX-2) upregulation. Treatment with celecoxib, an oral COX-2 inhibitor, helps reduce the incidence of HFS due to capecitabine. “However, it has not been adopted in the clinics due to concerns regarding cardiac and gastrointestinal toxicity,” according to the investigators.

*Diclofenac-topical for reduction of capecitabine related HFS