Photobiomodulation in the Treatment of Hand-foot Syndrome

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Erythrodysesthesia Syndrome

Intervention / Treatment
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* Device: Photobiomodulation
* Other: Moisturizer


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Group of participants will receive skin moisturizer and photobiomodulation sham while another group will receive the skin moisturizer and the active photobiomodulation treatment.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Moisturizing cream indicated and provided by the hospital (with urea) + LED treatment. | Device: Photobiomodulation<br>* 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.<br>* Other names: low-level laser therapy;Other: Moisturizer<br>* Both groups will receive moisturizer.<br>|
| Sham Comparator: Group 2<br>Moisturizing cream indicated and provided by the hospital (with urea) + LED sham treatment. | Other: Moisturizer<br>* Both groups will receive moisturizer.<br>|

What is the study measuring?
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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) | 
| HSF-14 | Quality of life questionnaire HSF-14 | Before treatment (Day 0) 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hand-Food Syndrome, Low-Level Light Therapy, Quality of life