Episode 11: Capecitabine: optimisation of dosing strategy and the use of topical diclofenac in prevention of hand-foot syndrome
Presented by Dr Kevin Punie (GZA Hospitals) and Prof Evandro De Azambuja (Institut Jules Bordet)
Capecitabine constitutes a pivotal therapeutic agent for breast cancer patients, employed in both early and advanced stages of the disease. Given its recognized toxicity profile, the optimization of dosing strategies is imperative to ensure optimal adherence.
The X-7/7 trial, presented at ASCO2023, featured a randomized, open-label investigation comparing two capecitabine dose regimens. The FDA-approved regimen involves administering 1250 mg/m² twice daily for 2 weeks, followed by a 1-week hiatus. This was compared to a dose-dense regimen of 1500 mg twice daily, employing a 7 days on/7 days off schedule.
The primary endpoint, 3-month PFS, exhibited no discernible difference between the regimens. Additional analyses on PFS and OS at different time points indicated comparable clinical outcomes. So using a fixed dose of capecitabine has similar survival compared to the standard dosing schedule.
Considering the commonly observed poor tolerance and high discontinuation rates associated with the standard dosing regimen, the safety profile of the investigated dose regimen emerged as a critical secondary endpoint. Notably, the dose-dense administration demonstrated a reduction in overall toxicity issues, with three times fewer grade 3-4 events in the experimental group, resulting in a three times lower discontinuation rate compared to the standard treatment.
HFS is a prevalent side effect of capecitabine, significantly impacting patients’ QoL. Another trial explored the efficacy of topically administered diclofenac in patients undergoing capecitabine treatment.
The experimental group applied a fingertip unit of 1% diclofenac ointment twice daily on the palms, while the control group applied a placebo.
The primary outcome, the incidence of grade 2 or higher HFS, was 15% in the placebo group and only 4% in the treatment group. This significant reduction in HFS incidence translated into a notable decrease from 15% to 4% in patients requiring a dose reduction of capecitabine treatment.
The experts concur that this study offers valuable tools for the management of HFS in patients undergoing capecitabine therapy, impacting clinical practice early on. The use of diclofenac in HFS development is evident not only in a preventive setting but also during active treatment.
Both studies contribute significantly to daily clinical practice, given the widespread use of capecitabine in breast cancer treatment and the effective preventive measures against one of its major debilitating side effects, HFS.
References:
Khan QJ. et al. (2023) Randomized trial of fixed dose capecitabine compared to standard dose capecitabine in metastatic breast cancer: The X-7/7 trial. Journal of Clinical Oncology 41:16_suppl, 1007.
Santhosh A. et al. (2023) Randomized double-blind, placebo-controlled study of topical diclofenac in prevention of hand-foot syndrome in patients receiving capecitabine. Journal of Clinical Oncology 41:16_suppl, 12005.