Timmins Hannah C, Li Tiffany, Trinh Terry, Kiernan Matthew C, Harrison Michelle, Boyle Frances, Friedlander Michael, Goldstein David, Park Susanna B
Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Prince of Wales Clinical School, University of New South Wales, Kensington, Australia.
Oncologist. 2021 May;26(5):366-374. doi: 10.1002/onco.13697. Epub 2021 Feb 10.
Paclitaxel treatment produces significant peripheral neuropathy, but the time course of neuropathy development and outcomes are unclear. Dose reduction is the only strategy to prevent neurotoxicity, however, the impact of dose-reduction on neuropathy outcomes remains unknown. This study aimed to prospectively evaluated neuropathy development from weekly paclitaxel treatment and evaluate the impact of dose-reduction on post-treatment neuropathy outcomes.
Breast cancer patients receiving paclitaxel (80mg/m ) weekly for 12-weeks were prospectively assessed using patient reported (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity; FACTGOG-Ntx), clinical (Total Neuropathy Score clinical version; TNSc) and neurophysiological measures up to 12-months post completion. The impact of dose-reduction on post-treatment (3.6 ± 0.1 months) clinical and patient reported outcomes was evaluated in 105 weekly paclitaxel-treated patients.
Significant neuropathy was present by 6-weeks across patient-reported, clinical, and objective neurophysiological assessments, increasing in prevalence and severity over the treatment course. Limited recovery occurred, with significant neuropathy being maintained up to 12 months (p < .05). Patients who received dose reduction had worse patient reported (FACT-GOG-Ntx: 40.2 ± .1.4) and clinical neuropathy outcomes (TNSc: 4.3 ± 0.4) compared to those who received the full dose (FACT-GOG-Ntx: 45.9 ± 0.9; TNSc: 3.3 ± 0.3, p < .05). Patients who ceased treatment early demonstrated the worse deficits (TNSc: 5.0 ± 0.6; FACT-GOG-Ntx: 37.3 ± 2.7) compared to those who received the complete dose (TNSc: 3.5 ± 0.3; FACT-GOG-Ntx: 45.3 ± 0.9, p < .05).
Weekly paclitaxel produces symptomatic and objective neuropathy early in the treatment course which can persist. Dose reduction does not necessarily lead to more favorable neuropathy outcomes, with individual risk factors likely important in addition to cumulative dose.
Weekly paclitaxel schedules are extensively used in breast cancer. Patients may develop symptomatic and objective neuropathy early in the treatment course, with these individuals requiring closer monitoring. Furthermore, neuropathy is a long-term sequela that may impact quality of life and require appropriate supportive services. Results suggest that dose reduction does not necessarily lead to better neuropathy outcomes. Understanding schedule-specific toxicity and risk factors for neuropathy will be critical to determining individualized treatment strategies and improving quality of life in breast cancer survivors.
紫杉醇治疗会产生严重的周围神经病变，但神经病变发展的时间进程和结果尚不清楚。降低剂量是预防神经毒性的唯一策略，然而，剂量降低对神经病变结果的影响仍然未知。本研究旨在前瞻性评估每周紫杉醇治疗引起的神经病变发展情况，并评估剂量降低对治疗后神经病变结果的影响。
对接受每周一次紫杉醇（80mg/m²）治疗12周的乳腺癌患者进行前瞻性评估，使用患者报告（癌症治疗功能评估/妇科肿瘤学组-神经毒性；FACTGOG-Ntx）、临床（总神经病变评分临床版；TNSc）和神经生理学测量，直至完成治疗后12个月。在105例接受每周紫杉醇治疗的患者中评估剂量降低对治疗后（3.6±0.1个月）临床和患者报告结果的影响。
在患者报告、临床和客观神经生理学评估中，6周时即出现明显的神经病变，在治疗过程中患病率和严重程度不断增加。恢复有限，严重神经病变一直持续到12个月（p＜0.05）。与接受全剂量治疗的患者相比，接受剂量降低治疗的患者患者报告的结果（FACT-GOG-Ntx：40.2±1.4）和临床神经病变结果（TNSc：4.3±0.4）更差（FACT-GOG-Ntx：45.9±0.9；TNSc：3.3±0.3，p＜0.05）。与接受完整剂量治疗者相比，提前停止治疗的患者表现出更严重的缺陷（TNSc：5.0±0.6；FACT-GOG-Ntx：37.3±2.7）（TNSc：3.5±0.3；FACT-GOG-Ntx：45.3±0.9，p＜0.05）。
每周一次紫杉醇在治疗早期即可产生有症状的和客观的神经病变，且这种病变可能持续存在。剂量降低不一定会带来更有利的神经病变结果，除累积剂量外，个体风险因素可能也很重要。
每周一次紫杉醇方案在乳腺癌治疗中被广泛应用。患者在治疗早期可能会出现有症状的和客观的神经病变，这些患者需要更密切的监测。此外，神经病变是一种长期后遗症，可能会影响生活质量，需要适当的支持性服务。结果表明，剂量降低不一定会带来更好的神经病变结果。了解特定方案的毒性和神经病变的风险因素对于确定个体化治疗策略和改善乳腺癌幸存者的生活质量至关重要。
