Study of Pyridoxine for Hand-Foot Syndrome

• ClinicalTrials.gov Identifier: NCT00446147
• Recruitment Status: Completed
• First Posted: March 12, 2007
• Results First Posted: February 25, 2014
• Last Update Posted: February 25, 2014
• Sponsor: Asan Medical Center
• Information provided by (Responsible Party): Yoon-Koo Kang, Asan Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hand-foot Syndrome	Drug: Pyridoxine; Drug: Placebo	Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 389 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Double-Blind Phase III Study of Pyridoxine vs Placebo for the Prevention of Capecitabine-induced Hand-Foot Syndrome
• Study Start Date: June 2004
• Actual Primary Completion Date: December 2006
• Actual Study Completion Date: December 2006

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; one tablet twice per day, which is identical to pyridoxine	Drug: Placebo; placebo 100mg BID/daily, Per oral
Experimental: Pyridoxine; 100 mg twice per day	Drug: Pyridoxine; 100mg BID/daily, Per oral

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Number of Patients With Hand-foot Syndrome [ Time Frame: Up to 2 years ]
   Number of patients with any grade of hand-foot syndrome

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Sponsors and Collaborators

Asan Medical Center

Investigators

• Principal Investigator: Yoon-Koo Kang; Asan Medical Center IRB

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kang YK, Lee SS, Yoon DH, Lee SY, Chun YJ, Kim MS, Ryu MH, Chang HM, Lee JL, Kim TW. Pyridoxine is not effective to prevent hand-foot syndrome associated with capecitabine therapy: results of a randomized, double-blind, placebo-controlled study. J Clin Oncol. 2010 Aug 20;28(24):3824-9. doi: 10.1200/JCO.2010.29.1807. Epub 2010 Jul 12.

• Responsible Party: Yoon-Koo Kang, Oncologist, Asan Medical Center
• ClinicalTrials.gov Identifier: NCT00446147
• Other Study ID Numbers: AMC-ONCGI-0403
• First Posted: March 12, 2007
• Results First Posted: February 25, 2014
• Last Update Posted: February 25, 2014
• Last Verified: January 2014

Keywords provided by Yoon-Koo Kang, Asan Medical Center:

hand-foot syndrome; capecitabine; pyridoxine; prevention

Additional relevant MeSH terms:

Hand-Foot Syndrome; Syndrome; Disease; Pathologic Processes; Drug Eruptions; Dermatitis; Skin Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Pyridoxine; Vitamin B Complex; Vitamins; Micronutrients; Physiological Effects of Drugs