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