Pyridoxine in Preventing Hand-Foot Syndrome Caused by Capecitabine in Patients With Cancer

• Time to the onset of HFS ≥ grade 2 [ Time Frame: days to weeks ] [ Designated as safety issue: No ]
• Quality of life as measured by EuroQOL (EQ-5D) questionnaire [ Time Frame: QOL assessment at baseline, at beginning of cycles 2, 4, 6, 8 and at the end of the study. ] [ Designated as safety issue: No ]

• Time to the onset of HFS ≥ grade 2
• Quality of life as measured by EuroQOL (EQ-5D) questionnaire

RATIONALE: Pyridoxine may help prevent hand-foot syndrome caused by capecitabine in patients with cancer. It is not yet known whether pyridoxine is more effective than a placebo in preventing hand-foot syndrome in patients with cancer.

PURPOSE: This randomized phase III trial is studying pyridoxine to see how well it works compared with a placebo in preventing hand-foot syndrome caused by capecitabine in patients with cancer.

OBJECTIVES:

Primary

• Compare the incidence of capecitabine-induced palmar-plantar erythrodysesthesia (hand-foot syndrome [HFS]) ≥ grade 2 in patients with cancer treated with pyridoxine hydrochloride vs placebo.

Secondary

• Compare the time to onset of HFS ≥ grade 2 in patients treated with these regimens.
• Compare the quality of life changes in patients treated with these regimens.
• Identify factors predicting toxicity from capecitabine chemotherapy.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to gender and treatment setting (adjuvant/neoadjuvant vs palliative setting). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Beginning concurrently with planned capecitabine treatment, patients receive oral pyridoxine hydrochloride once daily on days 1-21.
• Arm II: Beginning concurrently with planned capecitabine treatment, patients receive oral placebo once daily on days 1-21.

In both arms, treatment repeats every 21 days for up to 8 courses (until discontinuation of capecitabine treatment).

Quality of life is assessed at baseline, at the beginning of courses 2, 4, 6, and 8, and at the end of the study.

• Chemotherapeutic Agent Toxicity
• Dermatologic Complications
• Palmar-plantar Erythrodysesthesia
• Unspecified Adult Solid Tumor, Protocol Specific

• Dietary Supplement: pyridoxine hydrochloride
• Drug: capecitabine
• Procedure: complementary or alternative medicine procedure

DISEASE CHARACTERISTICS:

• Diagnosis of cancer
• Must be receiving single-agent capecitabine either in the adjuvant/neoadjuvant or palliative setting at a dose of ≥ 1000 mg/m² twice daily on days 1-14 (given in 3-week courses)

PATIENT CHARACTERISTICS:

• Life expectancy > 12 weeks
• No preexisting neuropathy
• No known allergy to pyridoxine hydrochloride and its incipients
• No other dermatologic condition that, in the opinion of the physician, may affect the hands or feet or may complicate evaluation during study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior capecitabine
• Concurrent radiotherapy, steroids, and/or biological therapy (e.g., trastuzumab [Herceptin®] or bevacizumab) allowed provided they do not cause hand-foot syndrome (HFS)
• No other concurrent drugs (e.g., docetaxel or doxorubicin hydrochloride liposome) that can cause HFS
• No concurrent drugs (e.g., oxaliplatin or taxanes) that can cause neuropathy
• No concurrent pyridoxine hydrochloride-containing preparations (e.g., multivitamins or vitamin B complex)
• No concurrent over-the-counter products that contain urea or lactic acid
• No concurrent drugs reported to have drug interactions with pyridoxine hydrochloride (e.g., cycloserine; hydralazine; immunosuppressants; isoniazid; levodopa; estrogen or estrogen-containing contraceptives; penicillamine; phenobarbitone; phenytoin; or pyrazinamide)