Efficacy of oxcarbazepine for prophylaxis against cumulative oxaliplatin-induced neuropathy.
ABSTRACT We conducted a randomized, open-label, controlled trial to assess the efficacy of oxcarbazepine for prophylaxis against oxaliplatin-induced peripheral neuropathy (OxIN). Thirty-two patients with colon cancer received 12 courses of the FOLFOX-4 regimen and were randomly assigned to receive oxcarbazepine (600 mg BID) or chemotherapy without oxcarbazepine. The incidence of OxIN was strikingly decreased in patients receiving oxcarbazepine (31.2% vs 75%). Oxcarbazepine may prevent OxIN symptoms. Further larger placebo-controlled trials are warranted to confirm our results.
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ABSTRACT: Oxaliplatin is a chemotherapeutic agent effective against advanced colorectal cancer. Unlike with other platinum-based agents, the main side effect of oxaliplatin is polyneuropathy. Oxaliplatin-induced polyneuropathy (OIPN) has a unique profile, which can be divided into acute and chronic neurotoxicity. Early identification of the neurotoxicity and alterations in dose or schedule for the medication could prevent the development of chronic symptoms, which, once established, may take many months or years to resolve or even persist throughout life with a substantial effect on quality of life. There is no doubt that the use of pharmacogenomic methods to identify genetic bases of interindividual differences in drug response has led to what is called tailoring treatment. Yet there are some challenges regarding the application of these differences. Many efforts have been made to prevent or treat OIPN. Better understanding of the mechanisms underlying the acute and chronic forms of OIPN will be a key component of future advances in the prevention and treatment of OIPN. The aim of this review is to highlight the clinical presentation, assessment, and management of OIPN, as well as the underlying pathophysiologic and pharmacogenomic background.Clinical Colorectal Cancer 11/2013; · 2.91 Impact Factor
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ABSTRACT: Colorectal cancer (CRC) is a significant health problem, with around 1 million new cases and 500000 deaths every year worldwide. Over the last two decades, the use of novel therapies and more complex treatment strategies have contributed to progressively increase the median survival of patients with unresectable advanced CRC up to approximately 30 mo. The availability of additional therapeutic options, however, has created new challenges and generated more complicated treatment algorithms. Moreover, several clinically important points are still in debate in first-line, such as the optimal treatment intensity, the most appropriate maintenance strategy, the preferred biologic to be used upfront in patients with KRAS wild-type CRC, and the need for more detailed information on tumor biology. In this moving landscape, this review analyses why the first-line treatment decision is crucial and how the choice may impact on further treatment lines. In addition, it focuses on results of major phase III randomized trials.World Journal of Gastroenterology 12/2013; 19(46):8474-8488. · 2.43 Impact Factor
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ABSTRACT: To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors. A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life. A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted.Journal of Clinical Oncology 04/2014; · 17.88 Impact Factor