2076P - Topical diclofenac for prevention of HFS in patients receiving capecitabine monotherapy: An exploratory subgroup analysis of the D-ToRCH phase III trial

Background

Hand foot syndrome is a distinct side effect associated with capecitabine. Celecoxib, a cyclooxygenase (COX 2) inhibitor is the only drug effective in randomized trials. However, its use in clinics has declined due to concerns regarding cardiac safety. In our trial, we describe the use of topical diclofenac for prevention of HFS in patients receiving capecitabine monotherapy.

Methods

The D torch trial randomized 264 patients with breast or GI cancers receiving capecitabine to apply either 1% topical diclofenac or placebo gel. Stratified permuted variable size block randomization was done using a computer-generated random numbers sequence. The primary objective was to compare the incidence of grade 2 or higher HFS in diclofenac and placebo arms. Secondary objectives were incidence of any grade HFS, capecitabine dose reduction due to HFS and adherence with application. Here, we report the results of the monotherapy subgroup.

Results

108 out of 264 patients received capecitabine monotherapy (56 in diclofenac arm and 52 in placebo arm). Baseline characteristics were well matched in both arms. The study group’s median age was 47 years (IQR 39.5-57.5). Majority were females (n=101, 93.5%). 67 patients (62%) had an ECOG performance status of 0-1, while the rest were PS 2. 95 patients (87.9%) had carcinoma breast and the remaining 13 patients had various gastrointestinal cancers. 63 patients (58.9%) and 41 patients (38.3%) had stage 3 and 4 disease respectively, whereas only 3 patients (2.8%) had stage 2 cancer. Overall, 12 patients developed grade 2 or higher hand foot syndrome, of which 2 were in diclofenac group and 10 were in placebo group (3.6% vs 19.2%, p=0.01). Any grade HFS was seen in 3 patients (5.4%) in diclofenac arm and 12 patients (23%) in placebo arm (p=0.008). Dose reductions of capecitabine were less frequent in the diclofenac arm compared to placebo (3.6% vs 19.2% p=0.01). Adherence to topical treatment was more in the diclofenac group compared to placebo (93.2% vs 82.2%, p=0.04).

Conclusions

Topical diclofenac gel significantly reduced the incidence of HFS in patients receiving capecitabine monotherapy. Topical diclofenac gel application led to less frequent dose reductions of capecitabine.

Clinical trial identification

CTRI/2021/01/030592 (Clinical Trials Registry of India).

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Alkem Laboratories.

Disclosure

All authors have declared no conflicts of interest.