Alpha-Lipoic Acid in Preventing Hearing Loss in Cancer Patients Undergoing Treatment With Cisplatin

• Ototoxicity measurement
• Malondialdehyde levels
• Serum α-lipoic acid levels

• Malondialdehyde levels, serum alpha-lipoic acid levels, tumor progression, toxicity, and response [ Time Frame: Baseline measurement will occur prior to first cisplatin treatment. Additional measurements will be completed before each subsequent cisplatin treatment. Follow-up measurement will occur at 1 and 3 months following the last cisplatin treatment. ] [ Designated as safety issue: No ]
• Serum alpha-Lipoic Acid [ Time Frame: A plasma determination of -lipoic acid will be conducted one of the Baseline or Follow-up visit to measure the absorption of -lipoic acid. ] [ Designated as safety issue: No ]
• Total Amount of Prescribed Cisplatin Dose Administered [ Time Frame: We will evaluate the placebo group versus the investigational drug group to determine if there is a significant difference in the amount of chemotherapy given as a result of a-lipoic acid supplementation. ] [ Designated as safety issue: No ]
• Response to Therapy [ Time Frame: After the 2nd cisplatin cycle, tumor size will be evaluated for progression. ] [ Designated as safety issue: Yes ]

• Tumor progression
• Toxicity
• Response

RATIONALE: Alpha-lipoic acid may prevent or lessen hearing loss caused by cisplatin.

PURPOSE: This randomized clinical trial is studying the effectiveness of alpha-lipoic acid in preventing hearing loss in cancer patients undergoing treatment with cisplatin.

OBJECTIVES:

Primary

Determine the ability of alpha-lipoic acid supplementation to prevent or reduce the incidence and severity of hearing loss in cancer patients undergoing treatment with cisplatin.

Secondary

Determine if this drug improves the oxidative state, as measured by a malondialdehyde measurement of oxidative stress, thereby protecting the patient against ototoxic-induced hearing loss.

OUTLINE: This is a placebo-controlled, double-blind, randomized, multicenter study. Patients are stratified by cancer stage and institution. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral alpha-lipoic acid supplement once a day beginning 1 week before the start of cisplatin treatment and continuing for up to 1 month after the completion of cisplatin. During cisplatin treatment, patients discontinue supplement 1 day prior to the cisplatin treatment and resume daily supplements 2 days post treatment.

Arm II: Patients receive oral placebo supplement once a day beginning 1 week before the start of cisplatin and continuing for up to 1 month after the completion of cisplatin. During cisplatin treatment, patients discontinue supplement 1 day prior to the cisplatin treatment and resume daily supplements 2 days post treatment.

Hearing and ototoxicity are assessed at baseline, on each day of chemotherapy, and at 1 and 3 months post chemotherapy.

Blood samples are collected periodically to measure malondialdehyde and alpha-lipoic acid levels.

After completion of treatment with cisplatin, patients are followed for 3 months.

• Ototoxicity
• Unspecified Adult Solid Tumor

• Drug: alpha-lipoic acid
  Supplements (1200mg once a day) or placebo will be administered to each patient prior to first cisplatin treatment and continue until 3 months after last treatment.
  Other Name: lipoic acid
• Behavioral: Audiology
  otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges.
  Other Name: ototoxicity monitoring
• Biological: laboratory biomarker analysis
  Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress.
  Other Name: MDA

• Experimental: 1
  Receiving alpha-lipoic acid during cisplatin treatment.
  Interventions:

  • Drug: alpha-lipoic acid
  • Behavioral: Audiology
  • Biological: laboratory biomarker analysis
• Placebo Comparator: 2
  Receiving placebo during cisplatin treatment
  Interventions:

  • Drug: alpha-lipoic acid
  • Behavioral: Audiology
  • Biological: laboratory biomarker analysis

Inclusion Criteria:

• Diagnosis of cancer
• Receiving therapeutic treatment with cisplatin
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• Cognitively and physically able to participate in the study
• Must be able to provide reliable behavioral threshold responses (patient must meet intra-session reliability criterion of +/- 5 dB)
• At least 6 months since prior treatment with cisplatin or other ototoxic medications (e.g., aminoglycoside antibiotics)
• At least 6 months since prior and no concurrent radiotherapy for head and neck tumors
• Concurrent radiotherapy targeted below the neck allowed
• More than 1 month since prior alpha-lipoic acid supplements

Exclusion Criteria:

• No aggressive behavior as indicated in electronic chart notes
• No documented dementia
• No Alzheimer's disease
• No severe psychosocial disorder
• No active or recent history of middle ear disorder based on otoscopy, tympanometry, immittance, or notes in patient chart
• No renal disease
• No Meniere's disease or retrocochlear disorder based on patient report or notes in patient's chart
• Not receiving treatment for diabetes mellitus
• No concurrent vincristine or vinblastine
• No other concurrent investigational therapy
• No other concurrent antioxidants or vitamin E > 100 IU per day