OBJECTIVES:

• Compare the efficacy of lamotrigine vs placebo in reducing pain and symptoms of chemotherapy-induced peripheral neuropathy in patients with cancer.
• Compare symptom distress, mood states, functional abilities, and overall quality of life of patients treated with these agents.
• Determine the toxic effects of lamotrigine in these patients.

OUTLINE: This is a randomized, placebo-controlled, double-blind study. Patients are stratified according to neurotoxic chemotherapy received (taxanes vs platinum-based compounds vs vinca alkaloids vs combination vs other), status of neurotoxic chemotherapy (actively receiving therapy vs discontinued or completed), and duration of pain or neuropathy symptoms (1-3 months vs 3-6 months vs more than 6 months). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral lamotrigine once daily for 2 weeks and then twice daily for 8 weeks.
• Arm II: Patients receive oral placebo once daily for 2 weeks and then twice daily for 8 weeks.

In both arms, treatment continues for 10 weeks in the absence of unacceptable toxicity.

Quality of life, pain, mood states, and symptom distress are assessed at baseline and at 4, 6, 8, and 10 weeks.

Patients are followed at 3-7 days.

PROJECTED ACCRUAL: A total of 120 patients (60 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of cancer

• Received, or are currently receiving, neurotoxic chemotherapy, including any of the following:

  • Taxanes (e.g., paclitaxel or docetaxel)
  • Platinum-based compounds (e.g., carboplatin, cisplatin, or oxaliplatin)
  • Vinca alkaloids (e.g., vincristine or vinblastine)

• Experiencing pain or symptoms of peripheral neuropathy for at least 1 month attributed to chemotherapy

  • Average daily pain rating of at least 4 out of 10 OR
  • Peripheral neuropathy at least grade 1 out of 3 using ECOG sensory neuropathy rating

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• At least 6 months

Hematopoietic

• Not specified

Hepatic

• Bilirubin < 2 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reaction or intolerance to lamotrigine
• No extreme difficulty swallowing pills

• No other identified causes of painful paresthesia preceding chemotherapy, including any of the following:

  • Radiation or malignant plexopathy
  • Lumbar or cervical radiculopathy

  • Pre-existing peripheral neuropathy of another etiology, such as any of the following:

    • Cyanocobalamin deficiency
    • AIDS
    • Monoclonal gammopathy
    • Diabetes
    • Heavy metal poisoning amyloidosis
    • Syphilis
    • Hyperthyroidism or hypothyroidism
    • Inherited neuropathy
• No significant psychiatric illness (e.g., mania, psychosis, or schizophrenia) that would preclude study participation
• Able to complete questionnaires

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• More than 7 days since prior methotrexate or other dihydrofolate inhibitors

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 7 days since prior, and no concurrent use of any of the following:

  • Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, or desipramine)

    • Concurrent selective serotonin reuptake inhibitors allowed
  • Monoamine oxidase inhibitors
  • Opioid analgesics
  • Anticonvulsants (e.g., gabapentin, topiramate, valproic acid, or clonazepam)

  • Adjuvant analgesics (e.g., mexiletine)

    • Prior nonsteroidal anti-inflammatory drugs allowed
  • Topical analgesics (e.g., lidocaine gel or patch) to the affected area
  • Amifostine
• More than 30 days since prior investigational agents for pain control
• No other concurrent investigational agents for pain control