Профилактический диклофенак не снижает риск синдрома «ладонь-стопа» у пациентов на терапией капецитабином

TOPLINE Prophylactic topical diclofenac does not reduce clinically significant hand-foot syndrome (HFS) in patients receiving capecitabine-based therapy, a new real-world observational study found. Grade ≥ 2 HFS occurred in approximately 17% vs 14% of patients using diclofenac gel vs those under active monitoring, with no difference in time to onset. METHODOLOGY - Capecitabine clinical utility is frequently compromised by HFS. The randomized phase 3 D-TORCH trial reported a reduction in grade ≥ 2 HFS with prophylactic topical diclofenac compared with placebo among patients receiving capecitabine monotherapy, but translation into routine clinical practice remains uncertain. - Researchers conducted a prospective, two-center observational study in Turkey between July 2023 and February 2024, enrolling 151 patients with colorectal or gastric cancer scheduled to receive capecitabine-based chemotherapy. - Patients were managed with either prophylactic 1% topical diclofenac gel applied twice daily to the hands and feet or active monitoring according to routine clinical practice, with treatment allocation determined by treating physicians. - HFS was assessed weekly using Common Terminology Criteria for Adverse Events version 5.0 by physicians not involved in treatment allocation decisions during a median follow-up of 19.1 weeks. The primary endpoint was incidence of grade ≥ 2 HFS, with secondary endpoints including time to onset of grade ≥ 2 HFS and capecitabine dose reductions attributable to HFS. - Capecitabine was administered as monotherapy in 26% of patients and in combination with oxaliplatin in 74%, with starting doses of approximately 1000 mg/m2 twice daily for 14 days every 21 days for systemic chemotherapy regimens. TAKEAWAY - Grade ≥ 2 HFS occurred in 12 (16.9%) of 71 patients receiving diclofenac and 11 (13.8%) of 80 patients under active monitoring, with no significant difference between groups (odds ratio [OR], 1.28; P = .591). - Time to onset of grade ≥ 2 HFS did not differ significantly between groups, with an exploratory median time to onset of 8.0 weeks vs 9.4 weeks. - HFS-related dose reductions occurred in 24 (33.8%) of 71 patients in the diclofenac group and 20 (25.0%) of 80 patients in the active-monitoring group (OR, 1.53; P = .235). - In multivariable analysis, female sex (OR, 3.87; P = .006) and capecitabine monotherapy (OR, 3.97; P =.005) were independently associated with grade ≥ 2 HFS. IN PRACTICE “In this prospective real-world study, prophylactic topical diclofenac did not reduce clinically significant capecitabine-induced HFS or delay its onset compared with active monitoring,” wrote the authors of the study. SOURCE The study was led by Orhun Akdogan, MD, Gazi University Faculty of Medicine, Ankara, Turkey. It was published online on August 20 in JCO Global Oncology. LIMITATIONS As an observational study with physician-directed treatment allocation, selection bias, residual confounding, and unmeasured baseline vulnerability cannot be excluded. Treatment-related heterogeneity, including systemic chemotherapy and chemoradiotherapy, may have influenced capecitabine exposure and toxicity risk. Adherence to topical diclofenac was based on patient self-report, follow-up duration varied across patients, and the number of grade ≥ 2 HFS events was limited. Although none of the observed deaths were considered related to topical diclofenac, the numerical imbalance in deaths between groups should be interpreted cautiously. Detailed pharmacogenetic analyses were beyond the scope of the study and represent an additional limitation in interpreting fluoropyrimidine-related toxicity risk. DISCLOSURES The study protocol was approved by the Ankara Etlik City Hospital Ethics Committee and conducted in accordance with the Declaration of Helsinki. Osman Sutcuoglu, MD, disclosed receiving honoraria from AstraZeneca; Bayer; and Nobelpharma Co., Ltd. No other potential conflicts of interest were reported by the authors. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.