NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule:

Hayakawa, Kazuhiro; Itoh, Takayuki; Niwa, Hideto; Mutoh, Tatsuro; Sobue, Gen

doi:10.1016/s0006-8993(98)00305-9

Cited by 53 publications

(30 citation statements)

References 23 publications

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“…In mice, NGF plays a key role in the recovery from numerous peripheral neuronal and non-neuronal insults, reducing or preventing neuropathy. 21,24,25 Ultrastructural evaluation of rat sciatic nerves revealed axonal damage without demyelination; similarly, we found amplitude alterations in the patients suggesting axonal demyelination. 26 ATRA is capable of reversing morphologic and functional changes due to peripheral neuropathy, by increasing NGF concentrations in nerve and serum.…”

Section: Statistical Analysis Continuous Variables Were Summarized Assupporting

confidence: 72%

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 Assupporting

confidence: 72%

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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“…Neurotrophic factors seem to provide an attractive approach to prevent and to treat CIN [2]. In animal models of cisplatin-, vincristineand taxol-induced neuropathy nerve growth factor (NGF) and insulin-like growth factor (IGF) were able to reduce or even prevent neuropathy [3,25,16]. Furthermore, a recent report on potent analgesic effects of gliaderived neurotrophic factor (GDNF) in neuropathic pain states suggests this compound may be an option for future treatment of CIN [6].…”

Section: Therapy Of Cin and Prophylactic Measuresmentioning

confidence: 99%

Chemotherapy-induced peripheral neuropathy

Quasthoff¹,

Hartung²

2002

J Neurol

836

552

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The induction of peripheral neuropathy is a common factor in limiting therapy with chemotherapeutic drugs. Little is known about the mechanisms responsible for the development of neuropathy. Depending on the substance used, a pure sensory and painful neuropathy (with cisplatin, oxaliplatin, carboplatin) or a mixed sensorimotor neuropathy with or without involvement of the autonomic nervous system (with vincristine, taxol, suramin) can ensue. Neurotoxicity depends on the total cumulative dose and the type of drug used. In individual cases neuropathy can evolve even after a single drug application. A general predisposition for developing a chemotherapy-induced neuropathy has been observed in nerves previously damaged by diabetes mellitus, alcohol or inherited neuropathy. The recovery from symptoms is often incomplete and a long period of regeneration is required to restore function. Up to now, no drug is available to reliably prevent or cure chemotherapy-induced neuropathy.

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“…Vinca alkaloids inhibit the outgrowth of neuritis and induce blockage of neural functions. 5 This is the first report that administration of VDS induced mydriasis caused by irritation of the sympathetic pathway.…”

Section: Figurementioning

confidence: 89%

Mydriasis after the treatment of vindesine in a patient with acute promyelocytic leukemia

et al. 2002

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NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule:

Cited by 53 publications

References 23 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

Chemotherapy-induced peripheral neuropathy

Mydriasis after the treatment of vindesine in a patient with acute promyelocytic leukemia

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