Neuroprotection During Chemotherapy

Abstract

The development of neurotoxicity during antineoplastic therapy is one of the most common reasons for termination or modification of cancer treatment. A number of different agents have been proposed to provide neuroprotection without affecting antitumor efficacy. This review provides an evidence-based summary of neuroprotective medicines, an overview of the literature relating to neuroprotection during cancer treatment and a Neurologist perspective risk assessment and management. Through a systematic review the authors identified 49 papers published to date that report human clinical trials involving potential neuroprotectants in adults. Case reports and series completed in a prospective fashion were also included. Sensory neuropathies were the most prevalent subtype in the literature, and most were at least partially reversible with or without neuroprotective treatment. The majority of study medications had minimal side effects, though 2 trials were prematurely terminated because of adverse patient outcomes. No study reported an effect on antitumor efficacy. Because of the variability in study design, cancer type, outcome measures, and clinical confirmation of neuropathy, meta-analysis could not be appropriately performed. We highlight risk factors and discuss neuropathy screening. Descriptive analysis is provided which reveals that many of the agents studied were likely to confer some at least some neuroprotective benefit.

Predictors of Chemotherapy-Induced Peripheral Neuropathy

“…Moreover, analgesic adjuvants used to relieve the symptoms of PN during chemotherapy did not show adequate prophylactic efficacy. Thus, in agreement with prior studies (Kannarkat et al, 2007;Ocean et al, 2004;Park et al,2008;Walker et al, 2007;Windebank et al, 2008;Wolf et al, 2008) it can be concluded that no effective analgesic adjuvants are currently available for CIPN. Verstappen et al reported that while neuropathic changes were observed in both dose intensity groups, the higher dose intensity group reported significantly more symptoms during therapy, whereas neurologic signs were significantly more p r o m i n e n t a f t e r a c u m u l a t i v e d o s e o f 1 2 m g v i n c r i s t i n e (Verstappen et al, 2005).…”

“…CIPN is a dose-limiting toxicity of chemotherapy that often develops in response to administration of various drugs, in particular, bortezomib, taxanes (paclitaxel, docetaxel), oxaliplatin and vincristine (Kannarkat et al, 2007;Ocean et al, 2004;Park et al,2008;Walker et al, 2007;Windebank et al, 2008;Wolf et al, 2008). However, effective strategies for preventing or treating CIPN are lacking.…”

“…Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of chemotherapy that often develops in response to administration of various drugs, including, molecularly targeted therapeutic agents (bortezomib), taxanes (paclitaxel, docetaxel), platinum compounds, platinum-containing drugs (cisplatin, carboplatin, oxaliplatin), vinca alkaloids (vincristine), thalidomide, lenalidomide, and epothilones (ixabepilone) (Kannarkat et al, 2007;Ocean et al, 2004;Park et al,2008;Walker et al, 2007;Windebank et al, 2008;Wolf et al, 2008). It has been postulated that CIPN may represent the initial stage in the development of neuropathic pain.…”

Chemotherapy-Induced Neuropathy

“…& Several other compounds have been evaluated in CIPN models, and some of them deserve to be mentioned because they could represent interesting candidates for future clinical testing [43,44]. & Acetyl-L-carnitine has shown promising results in several animal models of CIPN induced by oxaliplatin, cisplatin, paclitaxel, and vincristine.…”

Peripheral neurotoxicity of platinum-based chemotherapy

“…However, the clinical importance of a major toxic side effect of the currently available platinum drugs, that is, peripheral neurotoxicity, is under-represented. This is surprising, as platinum-induced sensory neuropathy can be a dose-limiting toxicity 2,3 and despite extensive efforts we are still unable to prevent or treat it 4,5 , as evidenced by the significant number of ongoing neuroprotection clinical trials focused on chemotherapy-induced peripheral neurotoxicity (for a detailed, although only partial, list see the United States National Institutes of Health website ClinicalTrials.gov).…”