Photobiomodulation in the treatment of palmar-plantar erythrodysesthesia

Background: Hand–foot syndrome is a frequent adverse effect of chemotherapy, particularly with capecitabine and 5-fluorouracil. It causes erythema, edema, desquamation, and pain, leading to decreased quality of life (QoL) and possible treatment discontinuation. Photobiomodulation (PBM) has demonstrated anti-inflammatory and analgesic effects in other chemotherapy-induced complications, suggesting a potential benefit for hand–foot syndrome. Objective: To evaluate the efficacy and safety of PBM using a red light-emitting diode in patients with chemotherapy-induced hand–foot syndrome. Design: A randomized, double-blind, two-arm clinical trial was conducted in Montevideo, Uruguay. Participants: 6 patients receiving capecitabine or continuous infusion 5-fluorouracil who developed and–foot syndrome were allocated 1:1 to PBM or sham treatment. Methods: PBM consisted of red LED light (630 nm, 4 J/cm², 20 cm² area, twice weekly for four weeks). Outcomes included HFS severity (WHO and CTC scales), pain, and quality of life (QoL/ HFS-14 and DLQI). Results: Six patients were enrolled (three per group). After treatment, both groups showed clinical improvement, with no difference between groups in success rates and greater mean reduction in HFS-14 scores in the PBM group (–23.5 ± 5.0, p < 0.001) than in the sham group (–9.8 ± 3.4, p = 0.02). No adverse events occurred. Conclusions: PBM was safe and well tolerated. Both PBM and sham groups showed within-group improvements in symptoms and quality of life; given the very small sample and early stop, between-group differences cannot be determined. The PBM non-responder patient exhibited concomitant chemotherapy-induced peripheral neuropathy, suggesting patients with substantial neuropathic involvement might require combined or alternative interventions. These pilot signals justify hypothesis-generating research with adequately powered trials. Registration: Clinical Trials prospective register no. NCT05337423. Countries of recruitment: Uruguay.