Groupe Hospitalier Universitaire, APHP site Saint-Louis-Université de Paris, Oncologie-Radiothérapie, Paris, France.
Groupe Hospitalier Universitaire, APHP site Pitié-Salpêtrière- Sorbonne Université, Electrophysiologie, Paris, France.
Int J Radiat Oncol Biol Phys. 2020 May 1;107(1):154-162. doi: 10.1016/j.ijrobp.2020.01.002. Epub 2020 Jan 24.
Radiation-induced (RI) plexopathy is a rare peripheral nerve injury after radiation therapy for cancer. No treatment has been shown to slow its progression. A pentoxifylline-vitamin E combination significantly reduced RI fibrosis, and its association with clodronate (PENTOCLO) allowed healing of osteoradionecrosis and reduction of neurologic symptoms in phase 2 trials.
A placebo-controlled, double-blind trial conducted in adults with RI limb plexopathy without cancer recurrence, randomized in 2 arms to PENTOCLO (pentoxifylline 800 mg, tocopherol 1000 mg, clodronate 1600 mg 5 days per week) or triple placebo. The primary outcome measure after 18 months of treatment was the neurologic Subjective Objective Management Analytic (SOMA) score evaluating pain, paresthesia, and motor disability.
Between 2011 and 2015, 59 patients were included: 1 false inclusion (neoplastic plexopathy), 29 treated with placebo (group P), and 29 treated with the active drugs (group A); 46 patients presented an upper-limb and 12 a lower-limb plexopathy. The mean delay after irradiation was 26 ± 8 years, for patients with neurologic symptoms for 5 ± 5 years. The median global SOMA scores in the P and A groups, respectively, were 9 (range, 6-11) versus 9 (range, 8-11) at M and 9 (range, 5-12) versus 10 (range, 6-11) at M without any significant difference. Analysis of the secondary outcomes showed that SOMA score subdomains for pain and paresthesia were more affected in group A (not significant). The frequency of adverse events was similar in the 2 groups (81% of patients): slight expected vascular-gastrointestinal symptoms in A, but a large excess of RI complications (arterial stenosis).
This first randomized drug trial in RI plexopathy failed to show a beneficial effect. More studies are needed in patients with less advanced disease and fewer confounding comorbidities and with a more sensitive measure to detect a therapeutic effect.
放射诱导性（RI）多神经病是癌症放射治疗后罕见的周围神经损伤。目前尚无治疗方法被证明能减缓其进展。己酮可可碱-维生素 E 联合显著减少 RI 纤维化，并且在 2 期试验中，己酮可可碱-维生素 E 联合氯膦酸二钠（PENTOCLO）可治愈放射性骨坏死并减轻神经症状。
一项在成人 RI 肢体多神经病患者中进行的安慰剂对照、双盲试验，这些患者无癌症复发，随机分为 2 组，分别接受 PENTOCLO（己酮可可碱 800mg，生育酚 1000mg，氯膦酸二钠 1600mg，每周 5 天）或三联安慰剂治疗。18 个月治疗后的主要结局测量指标是评估疼痛、感觉异常和运动障碍的神经学主观客观管理分析（SOMA）评分。
2011 年至 2015 年间，共纳入 59 例患者：1 例假纳入（肿瘤性多神经病），29 例接受安慰剂治疗（P 组），29 例接受活性药物治疗（A 组）；46 例为上肢多神经病，12 例为下肢多神经病。放疗后平均潜伏期为 26±8 年，神经症状出现时间平均为 5±5 年。P 组和 A 组的中位总 SOMA 评分分别为 M 时的 9（范围，6-11）与 9（范围，8-11）和 M 时的 9（范围，5-12）与 10（范围，6-11），无显著差异。次要结局分析显示，A 组 SOMA 评分的疼痛和感觉异常亚域受影响更明显（无统计学意义）。两组不良反应发生率相似（81%的患者）：A 组轻微预期的血管胃肠道症状，但 RI 并发症（动脉狭窄）大量增加。
这项 RI 多神经病的首次随机药物试验未能显示出有益效果。在疾病程度较轻、合并症较少的患者中，以及采用更敏感的测量方法以检测治疗效果的患者中，需要开展更多的研究。
