Topical diclofenac in prevention of capecitabine associated HFS in patients with breast cancer: An exploratory subgroup analysis of the D-ToRCH study.

Abstract

18 Background: Hand foot syndrome (HFS) is a dose-limiting side effect of capecitabine in patients with breast cancer. Celecoxib, an oral cyclo-oxygenase-2 (COX-2) inhibitor is effective in reducing the incidence of capecitabine associated HFS. However, it has not been adopted in the clinics due to concerns regarding cardiac and gastrointestinal toxicity. We report the efficacy of topical diclofenac in prevention of capecitabine associated HFS in patients with breast cancer. Methods: In the D-ToRCH (Diclofenac-topical for reduction of capecitabine related HFS) trial, we randomized 264 patients with breast or gastrointestinal cancers planned to receive capecitabine to apply either 1% topical diclofenac or placebo gel. Stratified (male or female; capecitabine monotherapy or combination therapy), 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 reductions due to HFS and self-reported adherence with application. Here, we report the exploratory subgroup analysis of patients with breast cancer. Results: The breast cancer subgroup included 148 patients (77 in drug arm and 71 in placebo arm). Baseline characteristics were similar in both arms. Median age of overall population was 47 years (IQR 39-56). 89 patients (60.1%) had an ECOG (Eastern Co-operative Oncology Group) performance status of 0-1, while the rest had a score of 2. Hypothyroidism was the most common comorbidity (n=24, 16.2%). Majority received capecitabine monotherapy (n=95, 64.2%). The most common additional chemotherapy drug used was lapatinib (n=42, 79.3%). 60 patients had stage 3 disease (40.8%) and 88 patients had metastatic breast cancer (59.5%). Overall, 20 patients developed any grade HFS, of which 6 were in the diclofenac arm and 14 in placebo arm (7.8% vs 19.7%, p=0.034). Grade 2/3 HFS events were noted in 3 patients (3.9%) in diclofenac arm and 11 patients (15.5%) in placebo arm (p=0.016). Capecitabine dose reductions were less frequent in the diclofenac arm compared to placebo (3.9% vs 15.5%). Adherence to topical treatment was similar in both the study arm. Other adverse events of capecitabine like diarrhea, mucositis and myelosuppression were similar in both the arms. Conclusions: Topical diclofenac gel significantly reduced the incidence of all grades of HFS in breast cancer patients receiving capecitabine. Applying topical diclofenac led to less frequent capecitabine dose reductions. 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. Clinical trial information: CTRI/2021/01/030592 .