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

OBJECTIVES:

Primary

• Determine the efficacy of duloxetine hydrochloride in cancer patients with painful chemotherapy-induced (taxane or platinum agent) peripheral neuropathy.

Secondary

• Determine the influence of this drug on peripheral neuropathy-related functional status and quality of life of these patients.
• Describe the differences in duloxetine hydrochloride efficacy when used to treat pain caused by chemotherapy-induced peripheral neuropathy based on the neurotoxic drug and class.

OUTLINE: This is a randomized, double-blind, placebo-controlled, crossover study. Patients are stratified according to prior neurotoxic agent (paclitaxel vs oxaliplatin vs other taxane agents without paclitaxel vs platinum agents [cisplatin] without oxaliplatin) and high risk for developing painful chemotherapy-induced peripheral neuropathy (no vs yes). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral duloxetine hydrochloride once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive an oral placebo once or twice daily in weeks 8-13.
• Arm II: Patients receive an oral placebo once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive oral duloxetine hydrochloride once or twice daily in weeks 8-13.

Patients complete pain and quality of life questionnaires, including the BPI-SF once weekly and FACT/GOG-NTX and EORTC QLQ-C30 questionnaires, in weeks 1, 6, 8, and 13.

After completion of study treatment, patients are followed for 2 weeks.

DISEASE CHARACTERISTICS:

• Diagnosis of cancer

• CNS malignancy allowed with the exception of leptomeningeal carcinomatosis
• Must have painful sensory chemotherapy-induced peripheral neuropathy (CIPN) resulting from prior treatment with single-agent taxane or platinum agents (paclitaxel, docetaxel, nab-paclitaxel, oxaliplatin, cisplatin) (may not have received drugs from both classes)

• CIPN > grade 1 as measured by NCI-CTCAE v 4.0
• Average neuropathic pain score ≥ 4
• Patients with the following illnesses known to cause peripheral neuropathy are eligible, provided they have no evidence of neuropathy from these illnesses:

• Diabetes mellitus
• Peripheral vascular disease
• HIV infection
• Significant degenerative or familial neurologic disorder known to cause peripheral neuropathy
• No clinical or subclinical neuropathy from nerve compression injuries (i.e., carpal tunnel syndrome, brachial plexopathy, spinal stenosis, or spinal nerve root compression)

PATIENT CHARACTERISTICS:

• AST ≤ 3 times upper limit of normal
• Total bilirubin ≤ normal
• Creatinine clearance > 30 mL/min
• Not pregnant or nursing
• Able to take oral or enteral medication
• No history of seizure disorder
• No diagnosis of ethanol addiction or dependence within the past 10 years
• No history of narrow-angle glaucoma
• None of the following:

• History of suicidal thoughts
• Symptoms of or history of schizophrenia, bipolar disease, or a major depression
• Serious eating disorder such as bulimia or anorexia where electrolyte imbalance is likely

PRIOR CONCURRENT THERAPY:

• At least 3 months since prior and no concurrent taxane or platinum agent
• At least 14 days since prior and no concurrent monoamine oxidase inhibitors or other antidepressants
• No other prior or concurrent neurotoxic drugs (e.g., vincristine, vinblastine, cytarabine, thalidomide, bortezomib, carboplatin, or procarbazine)
• No concurrent anticonvulsants
• No concurrent B or E vitamin supplementation in doses greater than the recommended daily allowance (RDA)

• Centrum (standard formula) and One-A-Day "essential" formula which contain 100% RDA for vitamins B6, E, and B12 allowed
• Other multivitamins allowed provided they contain no more than 100% RDA of B vitamins and vitamin E
• No concurrent treatment (pharmacologic) for depression