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新辅助治疗后紫杉醇、多西紫杉醇和脂质体紫杉醇在乳腺癌中的疗效和安全性分析。

Efficacy and safety analysis of paclitaxel, docetaxel and liposomal paclitaxel after neoadjuvant therapy in breast cancer.

机构信息

Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China.

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China.

出版信息

Breast Cancer Res Treat. 2020 Nov;184(2):397-405. doi: 10.1007/s10549-020-05851-8. Epub 2020 Aug 10.

Abstract

BACKGROUND AND PURPOSE

Paclitaxel-based regimens are widely used in the neoadjuvant therapy (NAT) of breast cancer. The purpose is to analysis the efficacy and adverse events (AEs) among common paclitaxel (PTX), docetaxel and liposomal paclitaxel. At the same time, we want to analysis the axillary nodal pathologic complete response (apCR) after NAT among the three groups.

METHODS

From April 2014 to 2020, 647 breast cancer patients underwent operation after NAT were included in this study. Patients received full course of anthracycline- and paclitaxel-based chemotherapy before surgery. The paclitaxel-based regimens included PTX, docetaxel and liposomal paclitaxel. The therapy efficacy and AEs of the three groups were evaluated. At the same time, the apCR was also analyzed.

RESULTS

In general, 30.6% (198/647) of patients achieved breast pathologic complete response (bpCR), which was 28.6%, 28.3% and 39.3% among PTX, docetaxel and liposomal paclitaxel group, respectively (p = 0.067). The total pathologic complete response (tpCR) (achieving both bpCR and apCR) was 21.6% (140/647). The tpCR was 13.3%, 19.4% and 34.4% among PTX, docetaxel and liposomal paclitaxel group, respectively (p = 0.026). The multivariate logistic analysis result showed that clinical tumor stage and molecular subtype were significantly associated with tpCR (all p < 0.05). Among 592 clinical positive patients (cN), the apCR was 39.0% (231/592). The multivariate logistic analysis showed that paclitaxel- based regimens and molecular subtype were indicated as independent predictors for apCR of NAT. The apCR was significantly higher in liposomal paclitaxel group (63.5%) than in PTX (24.6%) and docetaxel group (34.8%) (p < 0.001). The subgroup analysis among different molecular subtypes found that in triple negative (TN) and HER-2 positive (HER2+) subgroup, the apCR in liposomal paclitaxel group was significantly higher than those in PTX and docetaxel group (all p < 0.05). But no significant result was found in the subgroup analysis in hormone receptor positive/HER-2 negative subgroup (p = 0.050). Safety analysis indicated that the incidence of neutropenia (grade III-IV) and peripheral neurotoxicity (grade I-II) was significantly lower in the liposomal paclitaxel group than in the PTX and docetaxel group. The incidence of oral mucositis, anaphylaxis and palmar-plantar erythrodysesthesia syndrome was also much lower in liposomal paclitaxel than other two groups (all p < 0.05). And there was no significant difference in other AEs among the three groups (all p > 0.05).

CONCLUSION

Liposome paclitaxel had similar tumor suppressor effect compared with PTX and docetaxel in NAT setting. Moreover, it had a better axillary lymph node (ALN) response after NAT than PTX and docetaxel. These patients who received liposome paclitaxel had more chance to avoid ALN dissection after NAT. At the same time, the application of liposome enables liposome paclitaxel could significantly reduce AEs caused by chemotherapy. Therefore, we suggested the application of liposome paclitaxel in the NAT setting, especially for cN patients with TN and HER2 + disease.

摘要

背景与目的

紫杉醇类方案广泛应用于乳腺癌新辅助治疗(NAT)中。本研究旨在分析常见紫杉醇(PTX)、多西他赛和脂质体紫杉醇的疗效和不良事件(AEs),同时分析三组患者 NAT 后腋窝淋巴结病理完全缓解(apCR)情况。

方法

2014 年 4 月至 2020 年,共纳入 647 例接受 NAT 后手术的乳腺癌患者。所有患者在术前均接受了完整的蒽环类和紫杉醇类化疗。紫杉醇类方案包括 PTX、多西他赛和脂质体紫杉醇。评估三组患者的治疗效果和 AEs,同时分析 apCR。

结果

总体而言,30.6%(198/647)的患者达到了乳腺病理完全缓解(bpCR),PTX、多西他赛和脂质体紫杉醇组分别为 28.6%、28.3%和 39.3%(p=0.067)。总病理完全缓解(tpCR)(同时达到 bpCR 和 apCR)为 21.6%(140/647)。PTX、多西他赛和脂质体紫杉醇组分别为 13.3%、19.4%和 34.4%(p=0.026)。多因素逻辑回归分析结果显示,临床肿瘤分期和分子亚型与 tpCR 显著相关(均 p<0.05)。在 592 例临床阳性患者(cN)中,apCR 为 39.0%(231/592)。多因素逻辑回归分析显示,紫杉醇类方案和分子亚型是 NAT 中 apCR 的独立预测因素。脂质体紫杉醇组的 apCR 显著高于 PTX 组(24.6%)和多西他赛组(34.8%)(p<0.001)。不同分子亚型的亚组分析发现,在三阴性(TN)和人表皮生长因子受体 2 阳性(HER2+)亚组中,脂质体紫杉醇组的 apCR 显著高于 PTX 组和多西他赛组(均 p<0.05)。但在激素受体阳性/HER2 阴性亚组中,亚组分析未发现显著结果(p=0.050)。安全性分析表明,脂质体紫杉醇组的中性粒细胞减少(III-IV 级)和周围神经毒性(I-II 级)发生率显著低于 PTX 组和多西他赛组。脂质体紫杉醇组口腔黏膜炎、过敏反应和掌跖红斑感觉迟钝综合征的发生率也明显低于其他两组(均 p<0.05)。三组之间其他 AEs 的发生率无显著差异(均 p>0.05)。

结论

在 NAT 中,脂质体紫杉醇与 PTX 和多西他赛的肿瘤抑制作用相似,且 NAT 后腋窝淋巴结(ALN)反应优于 PTX 和多西他赛。接受脂质体紫杉醇治疗的患者在 NAT 后更有机会避免 ALN 清扫。同时,脂质体的应用使脂质体紫杉醇能够显著减少化疗引起的不良事件。因此,我们建议在 NAT 中应用脂质体紫杉醇,特别是对于 cN 患者中的 TN 和 HER2+疾病。

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