Beijers Antoinetta J M, Mols Floortje, Tjan-Heijnen Vivianne C G, Faber Catharina G, van de Poll-Franse Lonneke V, Vreugdenhil Gerard
Department of Internal Medicine, Máxima Medical Centre , Eindhoven and Veldhoven , The Netherlands.
Acta Oncol. 2015 Apr;54(4):463-9. doi: 10.3109/0284186X.2014.980912. Epub 2014 Nov 24.
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of oxaliplatin which can negatively influence quality of life. We aimed to study the influence of cumulative dose, dose schedule and dose reductions of adjuvant oxaliplatin on long-term severity and prevalence of CIPN among colorectal cancer (CRC) survivors.
In total 207 patients, diagnosed with CRC between 2000 and 2009 who underwent adjuvant treatment with oxaliplatin, were included. They completed the EORTC QLQ-CIPN20 2-11 years after diagnosis. Data on oxaliplatin administration and acute neuropathy during treatment were extracted from the medical files. Subscales were analyzed with analysis of covariance and neuropathy symptoms with logistic regression analysis.
Patients who received cumulative oxaliplatin dose of ≥ 842 mg/m(2) had a significantly worse EORTC QLQ-CIPN20 sensory score compared to those who received a low cumulative dose of < 421 mg/m(2) (mean 19 vs. 8; p = 0.02). They more often reported tingling toes/feet (13% vs. 2%, respectively; p = 0.01). Dose intensity and time delay did not influence the occurrence of CIPN. Patients receiving a dose reduction because of neuropathy (N = 50) reported a significantly worse sensory score at very similar cumulative doses, than those who did not receive a dose reduction because of neuropathy (N = 96) (mean 21 vs. 15; p = 0.01).
Cumulative dose of oxaliplatin is associated with long-term CIPN. The risk of developing long-term CIPN could only be reduced by decreasing the cumulative dose, whereas delay probably is not beneficial. Patients receiving a dose reduction because of acute neuropathy are still at risk of developing long-term CIPN. Future studies should focus on identifying patients who are at risk of developing CIPN.
化疗引起的周围神经病变(CIPN)是奥沙利铂的剂量限制性副作用,会对生活质量产生负面影响。我们旨在研究辅助性奥沙利铂的累积剂量、给药方案和剂量减少对结直肠癌(CRC)幸存者中CIPN的长期严重程度和患病率的影响。
总共纳入了207例在2000年至2009年间被诊断为CRC并接受奥沙利铂辅助治疗的患者。他们在诊断后2至11年完成了欧洲癌症研究与治疗组织(EORTC)QLQ-CIPN20问卷。从病历中提取奥沙利铂给药和治疗期间急性神经病变的数据。使用协方差分析对分量表进行分析,使用逻辑回归分析对神经病变症状进行分析。
接受奥沙利铂累积剂量≥842mg/m²的患者与接受低累积剂量<421mg/m²的患者相比,EORTC QLQ-CIPN20感觉评分明显更差(平均分别为19分和8分;p = 0.02)。他们更常报告脚趾/脚部刺痛(分别为13%和2%;p = 0.01)。剂量强度和时间延迟不影响CIPN的发生。因神经病变而接受剂量减少的患者(N = 50)在累积剂量非常相似的情况下,感觉评分明显比未因神经病变而接受剂量减少的患者(N = 96)更差(平均分别为21分和15分;p = 0.01)。
奥沙利铂的累积剂量与长期CIPN相关。只有通过降低累积剂量才能降低发生长期CIPN的风险,而延迟可能并无益处。因急性神经病变而接受剂量减少的患者仍有发生长期CIPN的风险。未来的研究应侧重于识别有发生CIPN风险的患者。