S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, Stage II, or Stage IIIA Breast Cancer Undergoing Chemotherapy

• Neurotoxicity as measured by the 11-item neurotoxicity component of the FACT-Taxane Questionnaire at baseline and at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  

• Functional status as measured by the FACT-Taxane Trial Outcome Index at baseline and at 12, 24, and 36 weeks [ Time Frame: 12, 24 and 36 weeks ] [ Designated as safety issue: No ]
  
• Fatigue as measured by the FACIT-Fatigue Symptom Module at baseline and at 12, 24, and 36 weeks [ Time Frame: 12, 24, and 36 weeks ] [ Designated as safety issue: No ]
  
• Proportion of patients experiencing grade 2 or 3 neuropathy as measured by NCI CTCAE v3.0 criteria at 12, 24, and 36 weeks [ Time Frame: 12, 24, and 36 weeks ] [ Designated as safety issue: Yes ]
  
• Nerve growth factor levels at baseline and 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  
• Total dose of taxane received and treatment delays, compliance with therapy, and use of concurrent medications, dietary supplements (e.g., glutamine), vitamin E, and complementary and alternative medicines [ Time Frame: 12, 24 and 36 weeks ] [ Designated as safety issue: No ]
  
• Relationship between nerve growth factor levels and the degree of neuropathy and functional status [ Time Frame: end of study ] [ Designated as safety issue: No ]
  
• Relationship between genetic markers responsible for taxane metabolism and clearance and degree of neuropathy [ Time Frame: end of study ] [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare whether treatment with acetyl-L-carnitine hydrochloride vs placebo prevents symptoms of neuropathy as measured by the 11-item neurotoxicity component of the FACT-Taxane Questionnaire at 12 weeks after study registration in women with stage I, II, or IIIA breast cancer undergoing adjuvant taxane-based chemotherapy.

Secondary

• Compare the functional status of these patients using the Trial Outcome Index from the FACT-Taxane Questionnaire.
• Compare fatigue in these patients using the FACIT-Fatigue Symptom Module.
• Compare the proportion of patients experiencing grade 2 or 3 neuropathy.
• Compare serum nerve growth factor levels in these patients.
• Describe the total dose of taxane received and treatment delays, compliance with therapy, and use of concurrent medications, dietary supplements (e.g., glutamine), vitamin E, and complementary and alternative medicines in these patients.
• Explore the relationship between nerve growth factor levels and the degree of neuropathy and functional status in these patients.
• Explore the relationship between genetic markers responsible for taxane metabolism and clearance (e.g., CYP2C8, CYP3A4, CYP3A5, GSTM1, and GSTP1) and the degree of neuropathy in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to planned adjuvant chemotherapy regimen for breast cancer (paclitaxel weekly for 12 weeks vs paclitaxel biweekly for 4 courses [8 weeks] vs paclitaxel biweekly for 6 courses [12 weeks] vs docetaxel every 3 weeks for 4 courses [12 weeks] vs docetaxel every 3 weeks for 6 courses [18 weeks]) and age (< 60 years vs ≥ 60 years). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral acetyl-L-carnitine hydrochloride 3 times daily for 24 weeks.
• Arm II: Patients receive oral placebo 3 times daily for 24 weeks. Patients complete the FACT-Taxane Trial Outcome Index and the FACIT-Fatigue Symptom Module questionnaires at baseline, at 12, 24, and 36 weeks, and at 1 and 2 years.

Blood samples are collected at baseline and at week 12 for biomarker analysis (nerve growth factor levels) by ELISA, DNA extraction, and genotyping analysis.