Clinical trial NCT00446147: Study of Pyridoxine for Hand-Foot Syndrome
Official title: Double-Blind Phase III Study of Pyridoxine vs Placebo for the Prevention of Capecitabine-induced Hand-Foot Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hand-foot Syndrome
Keywords: hand-foot syndrome
capecitabine
pyridoxine
prevention
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2007-03-12
Enrollment: 389
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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.

Primary outcomes:
measure: Cumulative Dose of Capecitabine Until the Development of Grade 2 or Higher Hand-foot Syndrome
timeFrame: Up to 2 years
Secondary outcomes:
measure: Number of Patients With Hand-foot Syndrome
timeFrame: Up to 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Asan Medical Center IRB
name: Yoon-Koo Kang
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.