Laboratorio de Oncología Experimental, Instituto Nacional de Cancerología, Tlalpan, Mexico.
Neurology. 2011 Sep 6;77(10):987-95. doi: 10.1212/WNL.0b013e31822e045c. Epub 2011 Aug 24.
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).
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.
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.
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.
This study provides Class II evidence that ATRA improves nerve conduction in patients with chemotherapy-induced peripheral neuropathy.
评估全反式维甲酸（ATRA）治疗化疗诱导的周围神经病的疗效，在实验动物模型和非小细胞肺癌（NSCLC）患者的随机、双盲、对照试验中进行评估。
40 只雄性 Wistar 大鼠随机分为 5 组：A 组，对照组；B 组和 C 组，用顺铂治疗；D 组和 E 组，用紫杉醇治疗。C 组和 E 组给予 ATRA（20mg/kg PO）治疗 15 天。我们评估了坐骨神经的神经病和神经再生相关形态变化、神经生长因子（NGF）浓度以及视黄酸受体（RAR）-α和 RAR-β的表达。此外，95 例接受化疗治疗的 NSCLC 患者随机分为 ATRA（20mg/m²/d）或安慰剂组。评估血清 NGF、神经生理测试和临床神经毒性。
实验动物出现神经病和轴突变性，与周围神经中 NGF 水平降低有关。ATRA 治疗逆转了感觉变化和神经形态；这与 NGF 水平升高和 RAR-β 表达增加有关。接受化疗的患者出现了临床神经病和神经生理学评估的轴突丢失，与 NGF 水平降低有关。ATRA 降低了神经传导速度和神经病变等级≥2 的临床症状表现的轴突变性。
ATRA 减轻了化疗诱导的实验性神经病，增加了 NGF 水平，并诱导了神经中的 RAR-β 表达。在患者中，血清 NGF 的减少与神经病的严重程度有关；ATRA 治疗降低了电生理改变。
这项研究提供了 II 级证据，表明 ATRA 改善了化疗诱导的周围神经病患者的神经传导。
