Photobiomodulation in the Treatment of Hand-foot Syndrome

Photobiomodulation in the Treatment of Palmar-plantar Erythrodysesthesia: Clinical, Randomized, Controlled Study

A cytotoxic complication caused by chemotherapy is hand-foot syndrome, also known as palmar-plantar erythrodysesthesia (PPE). The mechanism is not yet clear, but it is thought that the chemotherapeutic agent generates cytotoxicity on the acral epidermis. Clinically it manifests as erythema and edema on the palms of the hands and feet, dry and scaly skin, accompanied by a sensation of tightness and pain. Extreme cases present blisters and ulcerations that may require hospitalization. It can also be accompanied by paresthesias. The main objective will be to evaluate if photobiomodulation is effective in reducing PPE induced by Capecitabine and 5-Fluorouracil chemotherapy.

It will be a 4 week treatment, with 2 groups: G1 - Moisturizing cream and Photobiomodulation; G2: Moisturizing cream and photobiomodulation sham.

Study Overview

• Status: Terminated
• Conditions: Erythrodysesthesia Syndrome
• Intervention / Treatment: Device: Photobiomodulation; Other: Moisturizer

Detailed Description

Methodology: randomized, controlled, double-blind, single-center clinical trial. The study population (40 participants) will be divided into two groups - Group 1: moisturizer plus LED (light emitting diode) treatment and Group 2: moisturizer plus LED sham treatment. For the application of LED light, Antares (ibramed) with P2 LED cluster (630 nm) will be applied twice a week in the palmo-plantar areas of the hands and feet (4 J/cm2) for 4 weeks.

The Palmar-plantar Erythrodysesthesia (PPE) degree is the main outcome while the secondary outcomes are the data referring to the chemotherapy treatment plan (Chemotherapy dose, need of reducing drug dose or interrupting the treatment) and also the quality of life by using Hand-foot syndrome (HSF) questionnaire - HSF-14 and dermatology Life Questionnaire Index (DLQI). PPE grade and chemotherapy plan will be measured prior to the start of treatment with photobiomodulation, in the middle and at the end of it. Quality of life questionnaires (HFS-14 - Hand-foot syndrome and DLQI - dermatology Life Questionnaire Index) will be applied at the beginning and at the end of the treatment.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Uruguay
  • Montevideo, Uruguay, 11600
    • Centro de Asistencia del Sindicato Médico del Uruguay
  • Montevideo, Uruguay, 11600
    • Instituto Nacional del Cancer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• over 18 years of age,
• hospitalized or outpatients,
• with oncological pathology (confirmed by anatomo-pathological or cytological diagnosis)
• undergoing chemotherapy treatment (oral capecitabine and 5-Fluorouracil in continuous infusion, following the treatment plans protocolized by the institution: Xelox Bevacizumab, Capecitabine, Capecitabine + Radiotherapy, Folfoxiri, Xeliri-Bevacizumab, Folfox4-Bevacizumab , Docetaxel-CDDP-5-Fluorouracil (Colony Stimulating Factors), mFolfirinox q/14 days, Flot.)
• who develop hand-foot syndrome of greater or equal toxicity to 1 on the CTC scale NCI v. 5.0 and on Saif scale. Et al. for dark skin

Exclusion Criteria:

• Patients with palmo-plantar skin comorbidities,
• autoimmune comorbidities,
• amputated limbs,
• systemic infection,
• localized or regional limb infection,
• respiratory isolation,
• contact isolation
• insulin-requiring diabetics.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Moisturizing cream indicated and provided by the hospital (with urea) + LED treatment.	Device: Photobiomodulation; Group 1 will receive 630 nm LED and group 2 will receive sham treatment twice a week in the palmo-plantar areas of the hands and feet (4 J/cm2) for 4 weeks.; Other Names: low-level laser therapy; Other: Moisturizer; Both groups will receive moisturizer.
Sham Comparator: Group 2; Moisturizing cream indicated and provided by the hospital (with urea) + LED sham treatment.	Other: Moisturizer; Both groups will receive moisturizer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Palmo planar erythrodysesthesia grade	3 Epp grades were stablished by CTC NCI being: Grade 1 - Minimal palmoplantar skin changes, without pain (erythema, edema, hyperkeratosis),; grade 2 - Skin changes (scaling, blisters, fissures, edema, hyperkeratosis) with pain, limiting instrumental activities; grade 3 - Severe skin changes (scaling, blisters, fissures, edema, hyperkeratosis, bleeding), with pain..	Before treatment (Day 0), at half treatment (Day 14) and at the end of the treatment (Day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemotherapy dose	Total dose (mg) of chemotherapeutical drug used	Before treatment (Day 0), at half treatment (Day 14) and at the end of the treatment (Day 28)
Need of interrupting chemotherapy	The need of interrupting chemotherapy due to Palmo planar erythrodysesthesia : Yes or no	Before treatment (Day 0), at half treatment (Day 14) and at the end of the treatment (Day 28)
Need of reducting chemotherapy dose	The need of reducing dose of chemotherapy due to Palmo planar erythrodysesthesia: Yes or no	Before treatment (Day 0), at half treatment (Day 14) and at the end of the treatment (Day 28)
DLQI	Quality of life questionnaire - Dermatology life quality index	Before treatment ( Day 0) and the end of the treatment (Day 28)
HSF-14	Quality of life questionnaire HSF-14	Before treatment (Day 0) and at the end of the treatment (Day 28)
Questionnaire	Questionnaire developed by researchers evaluating parameters in hands and feet related to daily activities.	Follow up (day 60)
Peripheral Sensory Neuropathy World Health Organization (WHO) Scale	Peripheral Sensory Neuropathy World Health Organization (WHO) Scale Grade 0: No; grade 1: symptoms Presence of paresthesias and/ or decreased deep tendon reflexes; Grade 2: Severe paresthesias and/or light muscle weakness Grade 3: Intolerable paresthesias and/or marked weakness , Grade 4: Paralysis	Before treatment ( Day 0) and the end of the treatment (Day 28)
Peripheral Sensory Neuropathy Eastern Clinical Oncology Group (ECOG) Scale	Peripheral Sensory Neuropathy Eastern Clinical Oncology Group (ECOG) Scale Grade 0, None, or no change; Grade 1: Loss of deep tendon reflexes, mild paresthesias. Grade 2: Mild or moderate objective sensory loss; moderate paresthesias. Grade 3: Severe objective sensory loss, or paresthesias that interfere with function	Before treatment ( Day 0) and the end of the treatment (Day 28)

Collaborators and Investigators

• Sponsor: University of Nove de Julho
• Investigators: Principal Investigator: Valentina Lestido, Master, Universidad Catolica de Uruguay

Publications and helpful links

General Publications

• Lestido V, Rodriguez F, Rodriguez A, Pombo V, Barrios R, Pavani C. Photobiomodulation in the treatment of palmar-plantar erythrodysesthesia: a randomised controlled clinical study protocol. BMJ Open. 2024 Apr 23;14(4):e081459. doi: 10.1136/bmjopen-2023-081459.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): May 30, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: April 4, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Estimated): August 27, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Quality of life; Low-Level Light Therapy; Hand-Food Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome; Therapeutics; Laser Therapy; Phototherapy; Low-Level Light Therapy
• Other Study ID Numbers: UninoveUCU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared. The sharing will begin 3 months following article publication. Researchers who provide a methodologically sound proposal will receive the access. Proposals should be directed to chrispavani@gmail.com. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Time Frame: Beginning 3 months following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.Proposals should be directed to xxx@yyy. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Link to be included).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No