title: Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer.
abstract: 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-β 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-β 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-β expression in nerve. In patients, reduction of NGF in serum was associated with the severity of neuropathy; ATRA treatment reduced the electrophysiologic alterations.
  
  
  METHODS
  This study provides Class II evidence that ATRA improves nerve conduction in patients with chemotherapy-induced peripheral neuropathy.
authors.affiliation: Laboratorio de Oncología Experimental, Instituto Nacional de Cancerología, Tlalpan, Mexico. ogar@servidor.unam.mx
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Arrieta
authors.forename: N
authors.initials: N
authors.lastname: Hernández-Pedro
authors.forename: M C
authors.initials: MC
authors.lastname: Fernández-González-Aragón
authors.forename: D
authors.initials: D
authors.lastname: Saavedra-Pérez
authors.forename: A D
authors.initials: AD
authors.lastname: Campos-Parra
authors.forename: M Á
authors.initials: MÁ
authors.lastname: Ríos-Trejo
authors.forename: T
authors.initials: T
authors.lastname: Cerón-Lizárraga
authors.forename: L
authors.initials: L
authors.lastname: Martínez-Barrera
authors.forename: B
authors.initials: B
authors.lastname: Pineda
authors.forename: G
authors.initials: G
authors.lastname: Ordóñez
authors.forename: A
authors.initials: A
authors.lastname: Ortiz-Plata
authors.forename: V
authors.initials: V
authors.lastname: Granados-Soto
authors.forename: J
authors.initials: J
authors.lastname: Sotelo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011115:Polyneuropathies / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014212:Tretinoin