Study of Pyridoxine for Hand-Foot Syndrome

Study Overview
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Brief Summary
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Although pyridoxine has been used empirically for the prevention of capecitabine associated hand-foot syndrome (HFS), its efficacy needs to be demonstrated in prospective controlled trials. The investigators therefore performed a prospective randomized double-blind study to determine whether pyridoxine 200 mg/day can prevent the development of HFS when given concurrently with capecitabine. The investigators also tested the ability of pyridoxine to treat primary occurrence of grade 2-3 HFS.

Detailed Description
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Although pyridoxine has been used empirically for the prevention of capecitabine associated HFS, its efficacy needs to be demonstrated in prospective controlled trials. We estimated that the HFS rate with placebo and pyridoxine would be 0.35 and 0.18, respectively, and we therefore calculated that a sample size of 345 patients would be necessary to detect these hazard rates with an 80% power (β=0.2) and two-sided significance level of α=0.05. We assumed a follow up loss rate of 10%, thus requiring 380 patients to be randomized. Chemotherapy-naive patients with gastrointestinal tract cancers who were scheduled for capecitabine-containing chemotherapy were assigned to receive oral pyridoxine or placebo in randomized double-blind placebo controlled study. Pyridoxine 100 mg b.i.d was prescribed to the patients in the pyridoxine group, identical placebo 100 mg b.i.d was prescribed in the placebo group by the closed envelop randomization. Patients were stratified by chemotherapy regimen: capecitabine alone (X), capecitabine and cisplatin (XP), or docetaxel, capecitabine, and cisplatin (DXP). Patients were observed until NCI CTC grade 2 or 3 HFS developed or capecitabine-containing chemotherapy ended. Patients in the placebo group who developed grade 2 or 3 HFS were randomized to receive pyridoxine or placebo for the next chemotherapy cycle to determine whether pyridoxine could improve HFS, and the same treatment was continued for 2 chemotherapy cycles.

Official Title
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Double-Blind Phase III Study of Pyridoxine vs Placebo for the Prevention of Capecitabine-induced Hand-Foot Syndrome

Conditions
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Hand-foot Syndrome

Intervention / Treatment
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* Drug: Pyridoxine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gastrointestinal tract cancer patients treated with capecitabine-containing chemotherapy as a first-line treatment were randomly allocated to concurrent treatment with pyridoxine or placebo. All patients were 18 to 70 years old Had Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower An estimated life expectancy > 3 months Adequate bone marrow function, including white blood cell (WBC) count of >3500 cells/㎕ and platelet count of >100000/㎕ Adequate renal function (serum creatinine concentration <1.5 mg/㎗) Adequate liver function with (serum bilirubin concentration <1.5 mg/㎗, transaminase <3 times the upper normal limit, and serum albumin >2.5 mg/㎗). Exclusion Criteria: Previous treatment for HFS Hypersensitivity to pyridoxine A combination of other malignancies Serious illnesses or medical conditions Immune suppression or positive human immunodeficiency virus (HIV) serology Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>one tablet twice per day, which is identical to pyridoxine | Drug: Placebo<br>* placebo 100mg BID/daily, Per oral<br>|
| Experimental: Pyridoxine<br>100 mg twice per day | Drug: Pyridoxine<br>* 100mg BID/daily, Per oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Dose of Capecitabine Until the Development of Grade 2 or Higher Hand-foot Syndrome | A total administered dose of capecitabine until the development of grade 2 or higher hand-foot syndrome during the chemotherapy. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Hand-foot Syndrome | Number of patients with any grade of hand-foot syndrome | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hand-foot syndrome, capecitabine, pyridoxine, prevention