Vitamin E neuroprotection for cisplatin neuropathy

Pace, Andrea; Giannarelli, Diana; Galiè, Edvina; Savarese, Antonella; Carpano, Silvia; Giulia, M. Della; Pozzi, A.; Silvani, Antonio; Gaviani, Paola; Scaioli, V.; Jandolo, B.; Bove, Loredana; Cognetti, Francesco

doi:10.1212/wnl.0b013e3181d5279e

Cited by 182 publications

(119 citation statements)

References 24 publications

(28 reference statements)

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“…Recently, a neuroprotective effect of vitamin E against CIPN has been reported. 33 Pharmacologic studies are necessary to determine dose and duration of ATRA therapy in CIPN. We selected the doses used in this study based on previous experimental reports on tolerance.…”

Section: Statistical Analysis Continuous Variables Were Summarized Asmentioning

confidence: 99%

Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer

Arrieta¹,

Hernández‐Pedro²,

Aragón³

et al. 2011

Neurology

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Objective:To evaluate the effect of all-trans retinoic acid (ATRA) as treatment for chemotherapyinduced peripheral neuropathy in an experimental animal model and in a randomized, doubleblinded, controlled trial in patients with non-small-cell lung cancer (NSCLC). Methods:Forty male Wistar rats were randomized in 5 groups: group A, control; groups B and C, treated with cisplatin; and groups D and E, treated with paclitaxel. ATRA (20 mg/kg PO) was administered for 15 days in groups C and E. We evaluated neuropathy and nerve regenerationrelated morphologic changes in sciatic nerve, the concentration of nerve growth factor (NGF), and retinoic acid receptor (RAR)-␣ and RAR-␤ expression. In addition, 95 patients with NSCLC under chemotherapy treatment were randomized to either ATRA (20 mg/m 2 /d) or placebo. Serum NGF, neurophysiologic tests, and clinical neurotoxicity were assessed. Results:The experimental animals developed neuropathy and axonal degeneration, associated with decreased NGF levels in peripheral nerves. Treatment with ATRA reversed sensorial changes and nerve morphology; this was associated with increased NGF levels and RAR-␤ expression. Patients treated with chemotherapy had clinical neuropathy and axonal loss assessed by neurophysiology, which was related to decreased NGF levels. ATRA reduced axonal degeneration demonstrated by nerve conduction velocity and clinical manifestations of neuropathy grades Ն2.Conclusions: ATRA reduced chemotherapy-induced experimental neuropathy, increased NGF levels, and induced RAR-␤ expression in nerve. In patients, reduction of NGF in serum was associated with the severity of neuropathy; ATRA treatment reduced the electrophysiologic alterations. Classification of evidence:This study provides Class II evidence that ATRA improves nerve conduction in patients with chemotherapy-induced peripheral neuropathy. Neurology ® 2011;77:987-995 GLOSSARY ATRA ϭ all-trans retinoic acid; CI ϭ confidence interval; CIPN ϭ chemotherapy-induced peripheral neuropathy; CP ϭ cisplatin/paclitaxel; DM ϭ diabetes mellitus; NGF ϭ nerve growth factor; NSCLC ϭ non-small-cell lung cancer; OR ϭ odds ratio; QOL ϭ quality of life; qRT-PCR ϭ quantitative reverse transcriptase and real-time PCR; RAR ϭ retinoic acid receptor; RT ϭ radiation therapy.Platinum-based chemotherapy is the first-line therapy for non-small-cell lung cancer (NSCLC) and improves both survival and disease-related symptomatology. 1 However, chemotherapyinduced peripheral neuropathy is common and decreases quality of life (QOL) and may limit chemotherapy doses.2 Cisplatin promotes the formation of free radicals, while paclitaxel blocks axonal transport within peripheral nerves. As many as 38% of patients with NSCLC treated with these drugs develop a disabling sensory neuropathy. 3,4 Retinoids play a critical role in a variety of biological functions, particularly in epithelial and neural differentiation.5 Different types of retinoids possess variable selectivity to retinoidFrom the Laboratorio de Oncología Experimental (Ó ....

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Section: Statistical Analysis Continuous Variables Were Summarized Asmentioning

confidence: 99%

Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer

Arrieta¹,

Hernández‐Pedro²,

Aragón³

et al. 2011

Neurology

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“…The severity of neurotoxicity, measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters, was significantly lower in patients of the vitamin E group than in patients in the control group (2 versus 4.7) (Pace et al, 2003). Later, Pace and colleagues performed a 2 center, double-blind, randomized, placebo controlled study of cisplatin induced neuropathy in solid tumor patients (Pace et al, 2010). A total of 108 patients treated with cisplatin chemotherapy were randomly assigned to receive vitamin E (400 mg/day) or placebo orally.…”

Section: Vitamin Ementioning

confidence: 99%

“…Neurotoxicity was measured with Total Neuropathy Score, and revealed a mean score of 1.4 in the vitamin E group versus 4.1 in the placebo group (p < 0.01). On sensory nerve conduction study, mean sural and median sensory amplitudes were both significantly reduced in the control group, while only mildly reduced in the sural nerve and unchanged in the median nerve in the vitamin E group (Pace et al, 2010). Argyriou and colleagues conducted 3 randomized, open label with blind assessment, controlled trials to determine whether vitamin E has a neuroprotective effect in chemotherapyinduced peripheral nerve damage.…”

Section: Vitamin Ementioning

confidence: 99%

Peripheral Neuropathy in Ovarian Cancer

Pan¹

2012

Ovarian Cancer - Clinical and Therapeutic Perspectives

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“…Although normal pain relief does not reduce the pain associated with CIPN, no specific anti-inflammatory drug has been trialled as a protective agent. This is one of the main mechanisms of action that has been identified in the nutrients and the herbs trialled for CIPN that have shown a possible beneficial protective effect [233][234][235][236][237][238][239][240][241][242][243][244][245][246]. The anti-inflammatory component may or may not protect patients against CIPN but it would be an interesting aspect to investigate.…”

Section: Strengths and Weaknesses And Gaps In The Researchmentioning

confidence: 99%

“…Vitamin E was demonstrated to have positive results in three RCT's showing a significant reduction in the relative risk of cisplatin induced PN, especially ototoxicity [233][234][235][236]254]. However, a phase III multi-centre trial combining vitamin E with taxanes, cisplatin, carboplatin, oxaliplatin or combination concluded that vitamin E did not appear to reduce the incidence of sensory neuropathy [254].…”

Section: Vitamin Ementioning

confidence: 99%

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

Schloss¹

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Vitamin E neuroprotection for cisplatin neuropathy

Abstract: This study provides Class II evidence that vitamin E supplementation significantly reduces the relative risk of developing signs or symptoms of neurotoxicity (relative risk = 0.14) (95% confidence interval = 0.02-1.00, p < 0.05).

Cited by 182 publications

References 24 publications

Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer

Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer

Peripheral Neuropathy in Ovarian Cancer

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

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