Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan.
Department of Breast Medical Oncology, Cancer Institute Hospital of JFCR, Koto, Tokyo, Japan.
Breast. 2021 Feb;55:63-68. doi: 10.1016/j.breast.2020.12.002. Epub 2020 Dec 9.
Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin-bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX.
We compared three different doses of q3w nab-PTX (Standard: 260 mg/m [SD260] vs Medium: 220 mg/m [MD220] vs Low: 180 mg/m [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded.
One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42-1.28) in MD220 vs SD260, 0.77 (95% CI 0.47-1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56-1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180.
Intravenous administration of low-dose nab-PTX at 180 mg/m q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.
纳米白蛋白结合紫杉醇（nab-PTX）治疗的患者常出现化疗引起的周围神经病。我们进行了一项多中心随机对照研究，以评估 nab-PTX 的最佳剂量。
我们比较了三种不同剂量的 q3w nab-PTX（标准：260mg/m [SD260] 与中剂量：220mg/m [MD220] 与低剂量：180mg/m [LD180]）在 HER2 阴性转移性乳腺癌（MBC）患者中的应用。主要终点是无进展生存期（PFS）。使用逻辑回归模型估计三种剂量的 3/4 级神经病变发生率。如果 PFS 的风险比（HR）<0.75 或>1.33，则排除低剂量，并继续进行非劣效性剂量。然后，如果估计的 3/4 级神经毒性发生率超过 10%，则排除该剂量。
141 例患者被随机分配至 SD260（n=47）、MD220（n=46）和 LD180（n=48）组，中位 PFS 分别为 6.66、7.34 和 6.82 个月。MD220 与 SD260 的 HR 为 0.73（95%可信区间 [CI]：0.42-1.28），LD180 与 SD260 的 HR 为 0.77（95% CI 0.47-1.28），LD180 与 MD220 的 HR 为 0.96（95% CI 0.56-1.66）。SD260 劣于 MD220 并被排除。SD260 的 3/4 级神经毒性发生率为 29.5%，MD220 为 14.0%，LD180 为 5.9%。最终选择的剂量为 LD180。
MBC 患者静脉给予低剂量 180mg/m nab-PTX q3w 可能是一种具有良好疗效和毒性的最佳治疗方法。
