Hand-foot Syndrome
Conditions
Keywords
hand-foot syndrome, capecitabine, pyridoxine, 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.
Interventions
DRUGPyridoxine
100mg BID/daily, Per oral
DRUGPlacebo
placebo 100mg BID/daily, Per oral
Sponsors
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Dose of Capecitabine Until the Development of Grade 2 or Higher Hand-foot Syndrome | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Hand-foot Syndrome | Up to 2 years | Number of patients with any grade of hand-foot syndrome |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo one tablet twice per day, which is identical to pyridoxine
Placebo: placebo 100mg BID/daily, Per oral | 180 |
| Pyridoxine 100 mg twice per day
Pyridoxine: 100mg BID/daily, Per oral | 180 |
| Total | 360 |
Baseline characteristics
| Characteristic | Placebo | Pyridoxine | Total |
|---|---|---|---|
| Age, Customized Age_median | 56 years | 56 years | 56 years |
| Region of Enrollment Korea, Republic of | 180 participants | 180 participants | 360 participants |
| Sex: Female, Male Female | 76 Participants | 59 Participants | 135 Participants |
| Sex: Female, Male Male | 104 Participants | 121 Participants | 225 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 180 | 0 / 180 |
| serious Total, serious adverse events | 0 / 180 | 0 / 180 |
Outcome results
Primary
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.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Cumulative Dose of Capecitabine Until the Development of Grade 2 or Higher Hand-foot Syndrome | 70000 miligram per square meter |
| Pyridoxine | Cumulative Dose of Capecitabine Until the Development of Grade 2 or Higher Hand-foot Syndrome | 70000 miligram per square meter |
Secondary
Number of Patients With Hand-foot Syndrome
Number of patients with any grade of hand-foot syndrome
Time frame: Up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Patients With Hand-foot Syndrome | 55 participants |
| Pyridoxine | Number of Patients With Hand-foot Syndrome | 57 participants |