Gabapentin in Treating Peripheral Neuropathy in Cancer Patients Undergoing Chemotherapy

OBJECTIVES:

• Determine whether gabapentin improves the pain and other symptoms in cancer patients with chemotherapy-induced peripheral neuropathy.
• Determine the effect of this drug on symptom distress, mood states, functional abilities, and overall quality of life in these patients.
• Determine the toxic effects of this drug in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to neurotoxic chemotherapy (active vs nonactive and discontinued vs completed) and neurotoxic chemotherapeutic agents (vinca alkaloids vs taxanes vs platinum-based compounds vs combination of two or more of the above agents). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive titrating doses of oral gabapentin twice daily and then three times daily for 3 weeks. Patients then receive a fixed dose of oral gabapentin three times daily for 3 weeks. Patients cross-over to therapy as in arm II at week 8.
• Arm II: Patients receive titrating doses of oral placebo and then a fixed dose of oral placebo as in arm I. Patients cross-over to therapy as in arm I at week 8.

Quality of life is assessed at baseline and then at the end of weeks 6, 8, and 14.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Has received or is currently receiving neurotoxic chemotherapy, including taxanes (e.g., paclitaxel or docetaxel), platinum-based compounds (e.g., carboplatin, cisplatin, or oxaliplatin), or vinca alkaloids (e.g., vincristine or vinblastine)
• Pain or symptoms of peripheral neuropathy of at least 1 month duration attributed to chemotherapy-induced peripheral neuropathy

• Average daily pain rating of at least 4 out of 10 using the pain numerical rating scale (where 0 is no pain and 10 is the worst pain possible) OR
• Evidence of peripheral neuropathy of at least grade 1 out of 3 by ECOG Common

• Toxicity Criteria for sensory neuropathy
• No other identified causes of painful paresthesia existing prior to chemotherapy

• No radiotherapy-induced or malignant plexopathy
• No lumbar or cervical radiculopathy
• No pre-existing peripheral neuropathy of another etiology, including:

• B12 deficiency
• AIDS
• Monoclonal gammopathy
• Diabetes
• Heavy metal poisoning
• Amyloidosis
• Syphilis
• Hyperthyroidism or hypothyroidism
• Inherited neuropathy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Life expectancy:

• At least 6 months

Renal:

• Creatinine no greater than 1.5 times upper limit of normal

Other:

• No prior allergic reaction or intolerance to gabapentin
• No significant psychiatric illness (e.g., mania, psychosis, or schizophrenia) that would preclude study compliance
• No extreme difficulty swallowing pills
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Other:

• More than 30 days since prior investigational agent for pain control
• Concurrent selective serotonin reuptake inhibitors allowed
• Concurrent nonsteroidal anti-inflammatory drugs allowed
• No concurrent tricyclic antidepressant (e.g., amitriptyline, nortriptyline, or desipramine)*
• No concurrent monoamine oxidase inhibitor*
• No concurrent opioid analgesic*
• No other concurrent adjuvant analgesic (e.g., anticonvulsant, clonazepam, or mexiletine)*
• No concurrent topical analgesics (e.g., lidocaine gel or lidocaine patch)*
• No concurrent amifostine
• No concurrent investigational agent for pain control NOTE: * For pain or symptoms due to chemotherapy-induced peripheral neuropathy