Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Room 7-824, 700 University Avenue, Toronto, ON, M5G 1X6, Canada.
Faculty of Medicine, University of Toronto, Toronto, Canada.
Cancer Chemother Pharmacol. 2019 Dec;84(6):1195-1200. doi: 10.1007/s00280-019-03956-6. Epub 2019 Sep 13.
Oxaliplatin is widely used in the treatment of gastrointestinal malignancies. One of the most common and dose-limiting side effects of oxaliplatin is the chronic peripheral sensory neuropathy. The mechanism of this neurotoxicity is poorly understood and there are no effective preventive or treatment strategies, other than oxaliplatin dose interruption or reduction.
Colorectal cancer patients who completed FOLFOX at least 6 months prior to enrollment were eligible. EORTC QLQ-CIPN20 questionnaire was used for assessing self-reported neuropathic symptom. Blood samples and skin biopsies were obtained and analyzed for platinum.
Twelve patients were enrolled. The mean cumulative dose of oxaliplatin was 818 ± 54 mg/m, and the median time from last dose of oxaliplatin was 38.7 months (range: 7.2-65.6 months). The QLQ-CIPN20 sensory score was 18 or less in 10 patients and 19 and 25, respectively, in 2 patients. Platinum was detectable in plasma from 4/12 patients up to 63.3 months after the completion of FOLFOX. In all six patients with skin biopsies, platinum was present in the skin with imaging mass cytometry.
QLQ-CIPN20 scores and plasma platinum concentrations were not related to cumulative doses of oxaliplatin or interval from the last dose of oxaliplatin. Platinum was readily detectable in skin biopsies more than 60 months post-completion of FOLFOX. This is the first demonstration of platinum deposition in skin post-oxaliplatin treatment and it provides a possible mechanism for oxaliplatin-induced peripheral sensory neuropathy and its persistence.
奥沙利铂广泛用于胃肠道恶性肿瘤的治疗。奥沙利铂最常见且剂量限制的副作用之一是慢性周围感觉神经病变。这种神经毒性的机制尚不清楚，除了中断或减少奥沙利铂剂量之外，没有有效的预防或治疗策略。
在入组前至少完成 FOLFOX 6 个月的结直肠癌患者符合条件。使用 EORTC QLQ-CIPN20 问卷评估自我报告的神经病变症状。采集血样和皮肤活检进行铂分析。
共纳入 12 名患者。奥沙利铂的平均累积剂量为 818 ± 54mg/m，末次奥沙利铂剂量后中位时间为 38.7 个月（范围：7.2-65.6 个月）。10 名患者的 QLQ-CIPN20 感觉评分均为 18 或以下，2 名患者分别为 19 和 25。4/12 名患者的血浆中可检测到铂，时间在完成 FOLFOX 后长达 63.3 个月。在所有 6 名接受皮肤活检的患者中，成像质谱细胞术均显示皮肤中有铂。
QLQ-CIPN20 评分和血浆铂浓度与奥沙利铂的累积剂量或末次奥沙利铂剂量后的间隔时间均无关。在完成 FOLFOX 后 60 多个月的时间里，皮肤活检中仍可轻易检测到铂。这是奥沙利铂治疗后皮肤中铂沉积的首次证明，为奥沙利铂引起的周围感觉神经病变及其持续性提供了可能的机制。
