duloxetine in treating peripheral neuropathy caused by chemotherapy in patients with cancer

Conditions: Neurotoxicity; Pain; Peripheral Neuropathy; Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: duloxetine may lessen peripheral neuropathy caused by chemotherapy. it is not yet known whether duloxetine is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy. purpose: this randomized phase iii trial is studying duloxetine to see how well it works compared with a placebo 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.

Eligibility criteria:
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

Keywords: unspecified adult solid tumor, protocol specific neurotoxicity pain peripheral neuropathy