對(duì)于高風(fēng)險(xiǎn)早期乳腺癌，術(shù)前新輔助治療可以提高手術(shù)的可行性和成功率、減少術(shù)后復(fù)發(fā)風(fēng)險(xiǎn)。目前，紫杉類化療方案已被廣泛用于乳腺癌術(shù)前新輔助治療。不過，紫杉醇、多西他賽、脂質(zhì)體紫杉醇等常用紫杉類化療藥物對(duì)于乳腺癌術(shù)前新輔助治療的有效性和安全性究竟孰高孰低尚不明確。
2020年8月10日，德國(guó)施普林格旗下《乳腺癌研究與治療》在線發(fā)表山東第一醫(yī)科大學(xué)（山東省醫(yī)學(xué)科學(xué)院）山東省腫瘤防治研究院（山東省腫瘤醫(yī)院）畢釗、陳鵬、劉雁冰、趙桐、孫曉、宋現(xiàn)讓、王永勝等學(xué)者的研究報(bào)告，對(duì)乳腺癌術(shù)前紫杉醇、多西他賽、脂質(zhì)體紫杉醇新輔助治療的效果和不良事件進(jìn)行了比較。
該單中心回顧研究對(duì)2014年4月～2020年4月山東省腫瘤醫(yī)院647例乳腺癌術(shù)前新輔助治療后手術(shù)患者進(jìn)行回顧分析。這些患者手術(shù)前接受了蒽環(huán)類＋紫杉類完整療程化療。紫杉類治療方案包括紫杉醇、多西他賽、脂質(zhì)體紫杉醇。對(duì)三組患者的治療效果和不良事件進(jìn)行分析。同時(shí)，還分析了腋窩病理完全緩解。
結(jié)果，乳腺病理完全緩解198例（30.6%），三組患者的乳腺病理完全緩解比例相似（P=0.067）
紫杉醇組：28.6%
多西他賽組：28.3%
脂質(zhì)體紫杉醇組：39.3%
總體病理完全緩解（同時(shí)獲得乳腺病理完全緩解和腋窩病理完全緩解）140例（21.6%），脂質(zhì)體紫杉醇組患者的總體病理完全緩解比例顯著較高（P=0.026）
紫杉醇組：13.3%
多西他賽組：19.4%
脂質(zhì)體紫杉醇組：34.4%
多因素邏輯分析結(jié)果表明，總體病理完全緩解顯著相關(guān)因素包括：
腫瘤臨床分期（P<0.001）
腫瘤分子亞型（P<0.001）
對(duì)于592例臨床淋巴結(jié)陽性患者，腋窩病理完全緩解231例（39.0%），脂質(zhì)體紫杉醇組患者的腋窩病理完全緩解比例顯著較高（P<0.001）
紫杉醇組：24.6%
多西他賽組：34.8%
脂質(zhì)體紫杉醇組：63.5%
多因素邏輯分析結(jié)果表明，腋窩病理完全緩解獨(dú)立預(yù)測(cè)因素包括：
紫杉化療方案（P<0.001）
腫瘤分子亞型（P<0.001）
不同分子亞型的亞組分析結(jié)果表明，對(duì)于三陰性乳腺癌或HER2陽性乳腺癌，脂質(zhì)體紫杉醇組患者的腋窩病理完全緩解比例顯著較高（P=0.024、P<0.001）
紫杉醇組：33.3%、27.3%
多西他賽組：44.1%、46.4%
脂質(zhì)體紫杉醇組：77.8%、80.4%
不過，對(duì)于激素受體陽性乳腺癌或HER2陰性乳腺癌，三組患者的腋窩病理完全緩解比例相似（P=0.050）。
安全性分析表明，脂質(zhì)體紫杉醇組與紫杉醇組和多西他賽組相比，III～I(xiàn)V級(jí)中性粒細(xì)胞減少、I～I(xiàn)I級(jí)周圍神經(jīng)毒性、口腔黏膜炎、過敏反應(yīng)、手足綜合征的發(fā)生比例顯著較低（全部P<0.05），其他不良事件的發(fā)生比例相似（全部P>0.05）。
因此，該研究結(jié)果表明，對(duì)于乳腺癌術(shù)前新輔助治療患者，脂質(zhì)體紫杉醇與紫杉醇和多西他賽相比，腫瘤抑制作用相似，腋窩淋巴結(jié)緩解比例顯著較高，避免腋窩淋巴結(jié)清掃的機(jī)會(huì)較大，化療所致不良事件比例顯著較低，故建議脂質(zhì)體紫杉醇用于術(shù)前新輔助治療患者，尤其對(duì)于三陰性乳腺癌和HER2陽性乳腺癌臨床淋巴結(jié)陽性患者。
相關(guān)鏈接
Breast Cancer Res Treat. 2020 Aug 10. Online ahead of print.
Efficacy and safety analysis of paclitaxel, docetaxel and liposomal paclitaxel after neoadjuvant therapy in breast cancer.
Bi Z, Chen P, Liu YB, Zhao T, Sun X, Song XR, Wang YS.
Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China; Shandong Cancer Hospital and Institute, Shandong University, Jinan, Shandong, China.
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.
KEYWORDS: Breast cancer, Neoadjuvant therapy, Liposome, Paclitaxel, Pathologic complete response
PMID: 32776291
DOI: 10.1007/s10549-020-05851-8
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