AC-TH與TCH方案對HER-2過表達乳癌新輔助化療效果比較

2021-08-18 20:52馬騰史亞飛馬天怡王海波
青島大學學報(醫學版) 2021年3期
關鍵詞:放化療輔助

馬騰 史亞飛 馬天怡 王海波

[摘要] 目的

比較AC-TH方案(表柔比星、環磷酰胺序貫多西他賽及曲妥珠單抗)與TCH方案(多西他賽、卡鉑聯合曲妥珠單抗)新輔助化療對人類表皮生長因子受體2(HER-2)過表達乳癌的近期療效以及不良反應。

方法 AC-TH方案新輔助化療HER-2陽性乳癌病人35例,TCH方案新輔助化療HER-2陽性乳癌病人26例,觀察并比較兩組新輔助化療效果及不良反應。

結果 AC-TH組總有效(OR)率、臨床完全緩解(cCR)率、病理完全緩解(pCR)率分別為91.4%、31.4%、25.7%,TCH組OR率、cCR率、pCR率分別為80.8%、50.0%、38.5%,兩組比較差異均無顯著性(P>0.05)。兩組病人骨髓抑制、心臟毒性及其他不良反應差異無顯著性(P>0.05);AC-TH組病人化療后左心室射血分數較TCH組明顯下降,差異有統計學意義(t=2.112,P<0.05)。

結論 HER-2過表達乳癌的新輔助化療中,AC-TH方案與TCH方案近期療效相當,但TCH方案心臟功能損害較小。

[關鍵詞] 乳房腫瘤;放化療,輔助;人類表皮生長因子受體2;治療結果

[中圖分類號] R739.9

[文獻標志碼] A

[文章編號] 2096-5532(2021)03-0365-04

doi:10.11712/jms.2096-5532.2021.57.119

[開放科學(資源服務)標識碼(OSID)]

[網絡出版] https://kns.cnki.net/kcms/detail/37.1517.R.20210628.1618.001.html;2021-06-29 09:48:36

CLINICAL EFFECT OF AC-TH REGIMEN VERSUS TCH REGIMEN AS NEOADJUVANT CHEMOTHERAPY FOR HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2-POSITIVE BREAST CANCER

MA Teng, SHI Yafei, MA Tianyi, WANG Haibo

(Center of Diagnosis and Treatment of Breast Disease, the Affiliated Hospital of Qingdao University, Qingdao 266100, China)

[ABSTRACT]Objective To investigate the short-term efficacy and toxicity of AC-TH regimen (epirubicin and cyclophosphamide followed by docetaxel and trastuzumab) versus TCH regimen (trastuzumab combined with docetaxel and carboplatin) as the neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER-2)-positive breast cancer.

Methods A total of 35 patients with HER-2-positive breast cancer received neoadjuvant chemotherapy with AC-TH regimen and 26 patients with HER-2-positive breast cancer received neoadjuvant chemotherapy with TCH regimen, and the two groups were compared in terms of the efficacy and toxicity of neoadjuvant chemotherapy.

Results There were no significant differences between the AC-TH group and the TCH group in overall response rate, clinical complete response rate, and pathologic complete response rate (91.4%/31.4%/25.7% vs 80.8%/50.0%/38.5%, P>0.05). There were no significant differences in bone marrow suppression, cardioto-

xicity, and other toxicities between the two groups (P>0.05), and compared with the TCH group, the AC-TH group had a signi-

ficant reduction in left ventricular ejection fraction after chemotherapy (t=2.112,P<0.05).

Conclusion As the neoadjuvant chemotherapy for HER-2-positive breast cancer, AC-TH regimen is comparable to TCH regimen in terms of short-term efficacy, while TCH regimen has little cardiac damage.

[KEY WORDS]breast neoplasms; chemoradiotherapy, adjuvant; human epidermal growth factor receptor 2; treatment outcome

新輔助化療是近年來乳癌治療革命性的進展,美國乳房與腸道外科輔助治療研究組及國內外多項隨機試驗結果均證實新輔助化療可行[1-5]。目前,臨床針對人類表皮生長因子受體2(HER-2)陽性、三陰性以及腫瘤負荷大或具有高復發風險的乳癌病人,選擇術前新輔助化療已經成為共識[6],其中對于HER-2陽性乳癌,AC-TH(蒽環類藥物、環磷酰胺序貫紫杉類藥物及曲妥珠單抗)及TCH(紫杉類藥物、卡鉑聯合曲妥珠單抗)方案均為指南推薦的方案[7-8]。但關于這兩種方案對HER-2過表達乳癌病人新輔助化療的短期療效及不良反應是否存在差異尚不清楚。本研究觀察并比較TCH與AC-TH方案對HER-2過表達乳癌病人新輔助化療的效果和不良反應,現報告如下。

1 資料與方法

1.1 一般資料

2017年6月—2019年1月,選取于青島大學附屬醫院乳腺病診療中心接受新輔助化療的HER-2陽性乳癌病人61例,均為女性,年齡31~68歲,中位年齡52歲。其中完成AC-TH方案新輔助化療35例,TCH方案新輔助化療26例。病人納入標準:①術前經空心針穿刺、乳房包塊病理檢查確診為HER-2陽性乳癌,且包塊直徑>2 cm;②經全身CT及骨掃描檢測確認腫瘤無遠處轉移;③術前初始新輔助化療為TCH或AC-TH方案;④治療期間相關評價完整;⑤新輔助化療結束后接受乳癌改良根治術,術后組織病理療效評價完整。兩組病人一般資料比較差異無統計學意義 (P>0.05)。見表1。

1.2 治療方法

1.2.1 TCH組 多西他賽 75 mg/m2靜脈滴注,第1天;卡鉑的AUC取6 mg/(mL·min),靜脈滴注,第1天;曲妥珠單抗靜脈滴注,首次8 mg/kg,隨后6 mg/kg,第1天。每3周為1個周期,共6周期。

1.2.2 AC-TH組 多柔比星 60 mg/m2靜脈滴注,前4周期每個化療周期的第1天;環磷酰胺600 mg/m2靜脈滴注,前4周期每個化療周期的第1天;多西他賽75 mg/m2靜脈滴注,后4周期每個化療周期的第1天;曲妥珠單抗靜脈滴注首次為8 mg/kg,隨后以6 mg/kg于后4周期每個化療周期的第1天。每3周為1個周期,共8個周期。

兩組病人每周期化療前均行血常規、血液生化、心電圖、心臟超聲等檢查,評估有無新輔助化療禁忌證。所有病人分別于化療前 12、6 h 給予地塞米松口服,化療前 0.5 h 給予苯海拉明(20 mg)和地塞米松(10 mg)肌注預防過敏,化療同時使用保心、保肝、保胃等藥物,化療后酌情使用促粒細胞集落刺激因子。兩組病人每周期化療后通過查體和B超檢查評價腫瘤大小,若發現腫瘤未緩解及時調整化療方案或行手術治療。新輔助化療結束2~3周內進行手術治療,手術方式為乳癌改良根治術。

1.3 療效評價方法

化療后采用乳房MRI測量腫瘤大小,按照世界衛生組織制定的實體瘤療效評價標準評定療效。臨床完全緩解(cCR):臨床檢查腫瘤完全消失; 臨床部分緩解(PR):腫瘤體積縮小≥50%;病情穩定(SD):腫瘤體積縮小<50%或增加<25%;疾病進展(PD):腫瘤體積增加≥25%或出現新病灶[9]。總有效(OR)=cCR+PR。病理完全緩解(pCR):病理檢查手術標本中原發腫瘤區無癌細胞浸潤,同時腋窩淋巴結未見轉移。

1.4 統計學處理

應用SPSS 22.0軟件進行統計學分析。計量資料采用±s表示,數據間比較采用t檢驗;分類資料比較采用χ2檢驗或Fisher精確概率檢驗;等級資料比較使用秩和檢驗。以P<0.05為差異有統計學意義。

2 結? 果

2.1 兩組療效比較

AC-TH組和TCH組的OR率分別為91.4%(32/35)和80.8%(21/26),差異無統計學意義(P>0.05),兩組cCR率分別為31.4%(11/35)和50.0%(13/26),差異無顯著性(P>0.05);兩組pCR率分別為 25.7%(9/35)和 38.5%(10/26),差異無顯著性(P>0.05)。

2.2 兩組不良反應比較

兩組病人均出現不同程度的惡心嘔吐、腹瀉、脫發、過敏反應等不良反應,均可耐受;AC-TH組與TCH組不良反應差異無統計學意義(P>0.05)。見表2。經粒細胞集落刺激因子及促紅細胞生成素支持治療后,兩組病人血常規恢復正常后繼續治療。兩組心臟毒性不良事件發生率差異無統計學意義(P>0.05),但AC-TH組3例病人出現Ⅲ級心臟毒性;AC-TH組病人化療后左心室射血分數(LVEF)較TCH組明顯下降,差異有顯著意義 (t=2.112,P<0.05)。見表3。

3 討? 論

新輔助化療又稱術前化療,是指惡性腫瘤病人手術前進行全身性、系統性的細胞毒性藥物治療,以縮小腫瘤體積使原發病灶降期,降低細胞活力,減少其播散的可能性,以消除全身微小轉移灶,為手術創造有利條件。HER-2過表達乳癌具有生物學惡性度高、預后不良、生存期短等特點[10],HER-2陽性不僅是乳癌預后的高風險因素,同時也是治療的關鍵靶點[11]。近年來曲妥珠單抗在乳癌輔助治療和解救治療中的應用逐漸成為常規,HER-2陽性乳癌病人的預后獲得了明顯改善[12]。相關研究結果顯示,HER-2陽性病人新輔助化療階段應用曲妥珠單抗能夠顯著提高新輔助治療效果[13-16]。2017年美國國立綜合癌癥網絡(NCCN)及2018年中國臨床腫瘤學會(CSCO)乳癌診療指南均推薦,以AC-TH及TCH方案作為HER-2陽性乳癌新輔助治療的優選方案[7-8]。蒽環類細胞毒性藥物是是乳癌新輔助化療的基本藥物,研究顯示該類化療藥物的客觀有效率(ORR)為50%~85%,pCR率為0~24%[17]。紫杉醇及多西紫杉醇也是乳癌新輔助化療的有效藥物,有研究結果顯示,表柔比星聯合環磷酰胺序貫多西他賽用于乳癌新輔助化療的疾病緩解率、總有效率均較表柔比星聯合環磷酰胺明顯提高,pCR率提高近1倍[13,18]。

目前,pCR已經成為評價乳癌新輔助化療方案療效最重要的指標[19]。本文研究結果顯示,AC-TH組和TCH組pCR率分別為25.7%和38.5%,差異無統計學意義,提示兩種方案新輔助化療的近期療效大致相當。但AC-TH組中的蒽環類藥物與曲妥珠單抗均有心臟毒性[20-21]。國外有研究顯示,同時接受蒽環類藥物和曲妥珠單抗治療的病人發生心力衰竭或心肌病的風險比單獨使用蒽環類藥物的病人高[22-23]。SLAMON等[24]中位隨訪3年研究發現,與阿霉素和環磷酰胺序貫多西他賽和曲妥珠單抗的AC-TH方案比較,曲妥珠單抗聯合多西他賽和卡鉑的TCH方案近期及遠期療效均相似,而心臟毒性反應卻很少。COUDERT等[15]研究結果顯示,化療方案為多西他賽和(或)卡鉑聯合曲妥珠單抗,曲妥珠單抗術前為單周方案、術后為3周方案,臨床cCR率、PR率、pCR率與含蒽環類藥物的化療方案相似,但心臟毒性卻大大降低。

本研究兩組病人心臟毒性、骨髓抑制、脫發、惡心嘔吐等不良反應差異無顯著性。但值得注意的是,AC-TH組3例病人出現Ⅲ級心臟毒性,而TCH組未發現Ⅲ/Ⅳ級心臟毒性病人;且AC-TH組病人化療后LVEF較TCH組明顯下降。本文研究中所有不良反應經過對癥處理均緩解,無病人因無法耐受化療不良反應而停止化療或死亡。

綜上所述,在HER-2過表達乳癌的新輔助化療中,AC-TH方案與TCH方案的近期療效相當,但TCH方案適應證更為寬泛,對于心臟功能存在潛在危險的新輔助化療適應證病人,TCH方案安全性更好,值得臨床推廣。但本文研究樣本量較小,且遠期療效尚在隨訪觀察中,其結論的可靠性尚需進一步研究驗證。

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(本文編輯 黃建鄉)

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