Study of Pyridoxine for Hand-Foot Syndrome
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
|Official Title:||Double-Blind Phase III Study of Pyridoxine vs Placebo for the Prevention of Capecitabine-induced Hand-Foot Syndrome|
- Cumulative Dose of Capecitabine Until the Development of Grade 2 or Higher Hand-foot Syndrome [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]A total administered dose of capecitabine until the development of grade 2 or higher hand-foot syndrome during the chemotherapy.
- Number of Patients With Hand-foot Syndrome [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Number of patients with any grade of hand-foot syndrome
|Study Start Date:||June 2004|
|Study Completion Date:||December 2006|
|Primary Completion Date:||December 2006 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
one tablet twice per day, which is identical to pyridoxine
placebo 100mg BID/daily, Per oral
Other Name: Placebo
100 mg twice per day
100mg BID/daily, Per oral
Other Name: Pyridoxine
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.