Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer.
Neurology
; 77(10): 987-95, 2011 Sep 06.
Article
em En
| MEDLINE
| ID: mdl-21865574
OBJECTIVE: To evaluate the effect of all-trans retinoic acid (ATRA) as treatment for chemotherapy-induced peripheral neuropathy in an experimental animal model and in a randomized, double-blinded, 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 regeneration-related morphologic changes in sciatic nerve, the concentration of nerve growth factor (NGF), and retinoic acid receptor (RAR)-α and RAR-ß 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-ß 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 ≥2. CONCLUSIONS: ATRA reduced chemotherapy-induced experimental neuropathy, increased NGF levels, and induced RAR-ß 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polineuropatias
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Tretinoína
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Carcinoma Pulmonar de Células não Pequenas
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Modelos Animais de Doenças
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Neoplasias Pulmonares
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Antineoplásicos
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neurology
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Estados Unidos