Lamotrigine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

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.

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

Life expectancy

• At least 6 months

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:

Chemotherapy

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

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