Taieb Sarah, Trillet-Lenoir Véronique, Rambaud Loïc, Descos Louis, Freyer Gilles
Medical Oncology Unit, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
Cancer. 2002 May 1;94(9):2434-40. doi: 10.1002/cncr.10500.
Regimens combining oxaliplatin with fluorouracil and folinic acid are standard therapeutic options for patients with metastatic colorectal carcinoma. Oxaliplatin has a good safety profile, although it is responsible for dose-limiting neurotoxicity typically consisting of two distinct clusters of symptoms. Cold-induced distal paresthesiae occur during or shortly after infusion in most patients and are usually transient and mild. A persistent sensory peripheral neuropathy may develop with prolonged treatment, eventually causing superficial and deep sensory loss, sensory ataxia and functional impairment.
The authors report four cases of atypical neurotoxicity induced by oxaliplatin in patients treated for metastatic colorectal carcinoma. Two patients were male and two were female, with an age range of 52-59 years.
Three patients experienced Lhermitte sign and two experienced urinary retention. In all cases, the cumulative dose of oxaliplatin was higher than 1000 mg (range, 1248-2040 mg). Brain and spinal magnetic resonance imaging was performed in two patients and was normal. Somatosensory evoked potentials were recorded in two patients and suggested cervical dorsal column dysfunction. Symptoms resolved a few weeks after discontinuation of oxaliplatin.
Lhermitte sign may be induced via a neurotoxic effect on the ascending axons of these T-shaped neurons. An atonic bladder may be the result of damage to the sensory portion of the sacral reflex arc, either in the dorsal roots, as for example in diabetic neuropathy, or in the posterior columns, as in tabes dorsalis. Alternatively, it may result from a paralysis of the parasympathetic fibers that control the bladder musculature. It is unclear at present whether the micturition difficulties observed in patients in the current series are due to sensory neuropathy or to autonomic neuropathy, event if the former hypothesis seems more likely, as autonomic neuropathy has not been previously observed with oxaliplatin, and its association with cisplatin is exceedingly rare and controversial.
奥沙利铂联合氟尿嘧啶和亚叶酸的方案是转移性结直肠癌患者的标准治疗选择。奥沙利铂具有良好的安全性,尽管它会导致剂量限制性神经毒性,通常由两组不同的症状组成。大多数患者在输注期间或输注后不久会出现冷诱导的远端感觉异常,通常是短暂且轻微的。长期治疗可能会出现持续性感觉性周围神经病变,最终导致浅感觉和深感觉丧失、感觉性共济失调和功能障碍。
作者报告了4例接受转移性结直肠癌治疗的患者因奥沙利铂引起的非典型神经毒性病例。2例为男性,2例为女性,年龄在52 - 59岁之间。
3例患者出现莱尔米特征,2例出现尿潴留。在所有病例中,奥沙利铂的累积剂量均高于1000mg(范围为1248 - 2040mg)。2例患者进行了脑和脊髓磁共振成像,结果正常。2例患者记录了体感诱发电位,提示颈髓后柱功能障碍。停用奥沙利铂后几周症状缓解。
莱尔米特征可能是由于对这些T形神经元的上升轴突产生神经毒性作用所致。无张力膀胱可能是骶反射弧感觉部分受损的结果,损伤部位可能在背根,如糖尿病性神经病变,或在后柱,如脊髓痨。或者,它可能是控制膀胱肌肉组织的副交感纤维麻痹的结果。目前尚不清楚本系列患者中观察到的排尿困难是由于感觉神经病变还是自主神经病变,尽管前一种假设似乎更有可能,因为以前未观察到奥沙利铂引起自主神经病变,而且其与顺铂的关联极为罕见且存在争议。