Diclofenac prevents hand-foot syndrome side effect of capecitabine | ASCO 2023

Results presented at the 2023 meeting of the American Society of Clinical Oncology support the use of diclofenac to prevent hand-foot syndrome caused by capecitabine. A second study in metastatic breast cancer, reported on the same day, showed that capecitabine could be given in a fixed, less frequent dose, improving tolerability without compromising effectiveness.

Background

The chemotherapy capecitabine is a treatment option for multiple types and stages of breast cancer. Unlike many forms of chemotherapy, capecitabine is available in pill form so it can be taken at home without the frequent, extended hospital or clinic visits required for infusions. The drug has the advantage of not causing hair loss, but is associated with other side effects that interfere with quality of life, including diarrhea and hand-foot syndrome. People who do not experience burdensome side effects are able to take capecitabine for extended periods of time.

Hand-foot syndrome can cause redness, swelling, and pain in the hands and feet. While not life-threatening, the discomfort can interfere with daily activities. Reports vary, but as many as 75% of people taking capecitabine for cancer experience hand-foot syndrome. It is not unusual for people to stop taking capecitabine or reduce their dose because of hand-foot syndrome.

Diclofenac is a topical gel that you can buy in a drugstore without a prescription. It is a non-steroidal anti-inflammatory drug (NSAID) often used by people with arthritis.

Results

In the phase III D-TORCH clinical trial, diclofenac reduced the risk of developing grade 2 or 3 hand-foot syndrome by 75% compared to a placebo. The randomized, double-blind trial included 263 people with breast (56%) or gastrointestinal (44%) cancer. Half had metastatic disease.

Participants applied the gel regularly, according to specific instructions, for 12 weeks. Only five people (3.8%) using diclofenac developed grade 2 or higher hand-foot syndrome, as compared with 20 people (15%) using the placebo gel. The people in the diclofenac group who did develop hand-foot syndrome did so sooner than those in the placebo group. The benefit of diclofenac was consistent across subgroups.

A second study reported at the same meeting also addresses the tolerability of capecitabine. The X-7/7 clinical trial found that a fixed dose of capecitabine taken less often was as effective as the standard dose in women with metastatic breast cancer. People taking the fixed dose experienced fewer side effects — especially hand-foot syndrome, diarrhea, and oral mucositis.

The X-7/7 trial compared a 1500 mg dose of capecitabine taken on a 7-days-on, 7-days-off schedule to the standard 14-days-on, 7-days-off schedule. The standard dose can vary by person, based on body surface area.

Most people in the trial had hormone receptor-positive, HER2-negative breast cancer, but 11% had triple-negative breast cancer and 11% had HER2-positive breast cancer. Nearly two-thirds of participants were trying chemotherapy for the first time. Participants received regular bone and CT scans and reported side effects at medical visits.

What does this mean for you?

If you and your doctor are considering capecitabine to treat breast cancer, there’s now a new strategy to help prevent a difficult side effect. Even though diclofenac is sold in drugstores without a prescription, talk with your healthcare team about how best to use it.

It's important to know that this trial was focused on people who were starting capecitabine, and does not offer any guidance for people who are already taking it. In addition, the results presented here only address hand-foot syndrome caused by capecitabine, not hand-foot syndrome caused by other cancer drugs, according to the study author.

Based on what we heard at ASCO, the alternate dosing schedule for capecitabine is unlikely to change the FDA-approved standard dose immediately, but it may be incorporated into future clinical trials. If you are taking capecitabine or exploring it as an option, talk with your doctor about these results. This news may offer you and your doctor some treatment flexibility.