A Surprising Approach to Hand-Foot Syndrome After Chemotherapy: Diclofenac Gel

Hand-foot syndrome (HFS) is an adverse effect associated with various cancer medicines, particularly capecitabine , an oral chemotherapy drug taken as tablets. It typically causes painful redness and swelling of the hands and feet, sometimes with crusting and sores.

The World Health Organization (WHO) uses four levels to classify HFS symptoms by severity:

• Level 1: Abnormal sensations or tingling in the hands and feet.
• Level 2: Painless swelling or redness, with discomfort when walking or holding objects.
• Level 3: Inflammation and painful swelling of the palms, soles, toenails and the areas around the toenails.
• Level 4: Ulcer formation, peeling skin, severe pain, blistering, ingrown nails and nail loss.

Capecitabine is frequently used to treat gastrointestinal and breast cancers. HFS of varying severity occurs in 25-75% of patients receiving it. Although generally not life-threatening, it can substantially reduce quality of life. More importantly, HFS may require capecitabine dose reductions, potentially reducing overall treatment effectiveness. It leads to dose reduction in 10-25% of patients and complete treatment discontinuation in as many as 10%.

Previous studies suggested that oral nonsteroidal anti-inflammatory drugs (NSAIDs) might alleviate HFS. However, their adverse effects and limitations created a need for alternatives. Researchers therefore decided to study topical diclofenac, an NSAID applied to the skin. Products containing topical diclofenac include Diclomec Gel, Dikloron Gel and Voltaren Emulgel.

The results of this innovative study were presented at the 2023 ASCO (American Society of Clinical Oncology) Annual Meeting. They offer new hope for better management of capecitabine's adverse effects and helping patients stay on treatment longer.

Study Details

In the D-TORCH clinical trial, researchers treated patients with topical diclofenac to improve their Dermatological Function Scale (DFS). They observed significant reductions in the proportion developing grade 2 or higher HFS and in overall HFS incidence. These findings indicate that diclofenac can reduce HFS severity and frequency.

This development is important for improving patient experience and quality of life and keeping patients on effective treatments longer.

D-TORCH is the first study to examine the effectiveness of topical diclofenac in preventing grade 2 or higher HFS in patients with breast or gastrointestinal cancers receiving capecitabine, using a randomized clinical trial design. In this Indian study, 264 participants received either diclofenac or placebo gel.

The study found that:

• Grade 2 or higher HFS occurred in 3.8% of patients using topical diclofenac and 15% receiving placebo (P=0.003).
• All-grade HFS occurred in 6.1% versus 18.1%.
• Quality of life also declined less in the diclofenac group than with placebo between baseline and follow-up, defined as HFS development or 12 weeks.
• Capecitabine dose reductions due to HFS were approximately 3 times less frequent with diclofenac than with placebo (3.8% versus 13.5%), potentially having important implications for oncological benefit. Treatment adherence remained high in both groups, above 90%.

In conclusion, diclofenac used alongside capecitabine may reduce adverse effects and improve quality of life. This advance could help patients benefit from effective cancer treatment for longer and offer new hope in cancer care.