A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): A University of Rochester CCOP study of 462 cancer survivors
ABSTRACT Chemotherapy-induced peripheral neuropathy (CIPN) occurs in as high as 70 % of patients receiving certain types of chemotherapy agents. The FDA has yet to approve a therapy for CIPN. The aim of this multicenter, phase III, randomized, double-blind, placebo-controlled trial was to investigate the efficacy of 2 % ketamine plus 4 % amitriptyline (KA) cream for reducing CIPN.
Cancer survivors who completed chemotherapy at least 1 month prior and had CIPN (>4 out of 10) were enrolled (N = 462). CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average "pain, numbness, or tingling in [their] hands and feet over the past 24 h" on an 11-point numeric rating scale at baseline and 6 weeks post intervention. ANCOVA was used to measure differences in 6-week CIPN with effects including baseline CIPN, KA treatment arm, and previous taxane therapy (Y/N).
The KA treatment showed no effect on 6-week CIPN scores (adjusted mean difference = -0.17, p = 0.363).
This study suggests that KA cream does not decrease CIPN symptoms in cancer survivors.
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ABSTRACT: Topical analgesics may play an important role in the management of chronic pain and have good tolerability. Systemic ketamine has limited usage as an anaesthetic and along with its potential for addiction and dependence has not gained popularity as an analgesic compound. Topical ketamine however, is devoid of serious side effects, and thus can be used in the management of various pain states such as neuropathic pain and complex regional pain syndrome. Despite using high concentrations of topical ketamine, clinically significant side effects are rare. The measured plasma levels of ketamine and norketamine in various studies were mostly below the threshold of detection. Topical ketamine has been used as compounded formulations alone in concentrations from 0.5% to 20% or in combination with other (co) analgesics. Its efficacy may depend on the choice of vehicle, the concentration and the pain state. Suboptimal concentration of ketamine and suboptimal pharmaceutical properties of the cream base might have contributed to the negative results of some studies. In this article we will review clinical studies involving the use of topical ketamine for pain.Minerva anestesiologica 05/2014; 81(4). · 2.13 Impact Factor
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ABSTRACT: Opinion statement: Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated with multiple chemotherapeutic agents. CIPN may have a detrimental impact on patients' quality of life and functional ability, as well as result in chemotherapy dose reductions. Although symptoms of CIPN can improve with treatment completion, symptoms may persist. Currently, the treatment options for CIPN are quite limited. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, has the most evidence supporting its use in the treatment of CIPN. Other agents with potential benefit for the treatment of established CIPN include gabapentinoids, venlafaxine, tricyclic antidepressants, and a topical gel consisting of the combination of amitriptyline, ketamine, and baclofen; none of these, however, has been proven to be helpful and ongoing/future studies may well show that they are not beneficial. The use of these agents is often based on their efficacy in the treatment of non-CIPN neuropathic pain, but this does not necessarily mean that they will be helpful for CIPN-related symptoms. Other nonpharmacologic interventions including acupuncture and Scrambler therapy are supported by positive preliminary data; however, further larger, placebo-controlled trial data are needed to confirm or refute their effectiveness.Current Treatment Options in Oncology 08/2014; 15(4). DOI:10.1007/s11864-014-0303-7 · 3.24 Impact Factor
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ABSTRACT: Introduction: The worldwide number of patients suffering from diabetes mellitus (DM) is projected to approach 552 million by the year 2030. As diabetic neuropathy (DN) is present in 8% of new diabetic patients at the time of diagnosis and occurs in ∼ 50% of all patients with established DM, the number of patients who will develop painful DN will also increase. The suboptimal efficacies of currently approved drugs have prompted investigators to develop new therapeutic agents for the management of painful DN.Areas covered: In this review, the authors present and elucidate the current status of drugs under investigation for the treatment of painful DN. A short synopsis of currently approved drugs is also given. Literature information and data analysis were retrieved from PubMed, the American Diabetes and Neurological Associations Websites and ClinicalTrials.gov. The keywords used in the search included: DM, DN, painful diabetic neuropathy.Expert opinion: In addition to treating the pain associated with DN, the actual causes of the disease should also be targeted for improved management. It is hoped that drugs which improve vascular blood flow, induce neural regeneration, reduce hyperglycemia, oxidative stress and inflammation can be more effective for the overall treatment of painful DN.Expert Opinion on Investigational Drugs 08/2014; 24(1). DOI:10.1517/13543784.2014.954033 · 5.53 Impact Factor