METHODS: This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial: the
Diclofenac Topical in Reducing
Capecitabine induced HFS (D-TORCH) study. A total of 264 patients with breast and gastrointestinal
malignancies will be randomly allocated (stratified by sex and type of
therapy [monotherapy or combination regimen with
capecitabine]) to receive either 1% topical
diclofenac or placebo that will be applied over the palmar and dorsal surface of the hands twice daily whilst taking
capecitabine for 12 weeks. The patients will be followed up until the end of four cycles. The primary objective of this study is to compare the effect of topical
diclofenac with placebo in preventing HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS). The secondary objective is to compare the effect of topical
diclofenac with placebo on preventing all grades of HFS (incidence of NCI CTCv5.0 all grade HFS), time to develop HFS (from the start of
capecitabine), patient-reported outcomes (PROs) (HF-HRQoL questionnaire), adherence with the application (self-reported),
capecitabine dose changes (number of patients with dose modifications due to HFS) and safety profile (NCICTCv5.0 all grade HFS) DISCUSSION: The D-TORCH study aims to determine if 1% topical
diclofenac reduces the incidence of grade 2 or higher HFS in patients receiving
capecitabine. To date, there have been a lot of trials for
hand-foot syndrome prevention using agents like
pyridoxine,
vitamin E,
carvedilol, and various polyherbal formulations, but none has been found successful. If the trial meets the primary end point, 1% topical
diclofenac will be the new standard of care for HFS prevention.
TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/2021/01/030592 . Prospectively registered on January 19, 2021.