Randomized trial of preoperative docetaxel with or without capecitabine after 4 cycles of 5-fluorouracil-epirubicin-cyclophosphamide (FEC) in early-stage breast cancer: exploratory analyses identify Ki67 as a predictive biomarker for response to neoadjuvant chemotherapy

被引：48

作者：

Ohno, S. ^{[1
,2
]}

Chow, L. W. C. ^{[3
]}

Sato, N. ^{[4
]}

Masuda, N. ^{[5
]}

Sasano, H. ^{[6
]}

Takahashi, F. ^{[7
]}

Bando, H. ^{[8
]}

Iwata, H. ^{[9
]}

Morimoto, T. ^{[10
]}

Kamigaki, S. ^{[11
]}

Nakayama, T. ^{[11
]}

Nakamura, S. ^{[12
]}

Kuroi, K. ^{[13
]}

Aogi, K. ^{[14
]}

Kashiwaba, M. ^{[15
]}

Yamashita, H. ^{[16
]}

Hisamatsu, K. ^{[17
]}

Ito, Y. ^{[18
]}

Yamamoto, Y. ^{[19
]}

Ueno, T. ^{[20
]}

Fakhrejahani, E. ^{[20
]}

Yoshida, N. ^{[20
]}

Toi, M. ^{[20
]}

机构：

[1] Kyushu Natl Canc Ctr, Div Clin Oncol, Fukuoka, Japan

[2] Kyoto Technosci Ctr, OOTR Inst, Kyoto 6068305, Japan

[3] Unimed Med Inst, Wanchai, Hong Kong, Peoples R China

[4] Niigata Canc Ctr Hosp, Dept Surg, Niigata, Japan

[5] Osaka Natl Hosp, Dept Surg, Breast Oncol Unit, Osaka, Japan

[6] Tohoku Univ, Sch Med, Dept Pathol, Sendai, Miyagi 980, Japan

[7] Kitasato Univ, Sch Pharm, Dept Clin Med Biostat, Tokyo, Japan

[8] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Breast & Endocrine Surg, Tsukuba, Ibaraki, Japan

[9] Aichi Canc Ctr Hosp, Dept Breast Oncol, Nagoya, Aichi 464, Japan

[10] Yao Municipal Hosp, Dept Breast Surg, Yao, Japan

[11] Sakai City Hosp, Dept Mammary Gland & Internal Secret Surg, Sakai, Osaka, Japan

[12] St Lukes Int Hosp, Dept Breast Surg Oncol, Tokyo, Japan

[13] Tokyo Metropolitan Komagome Hosp, Dept Surg, Div Clin Trials & Res, Tokyo, Japan

[14] NHO Shikoku Canc Ctr, Dept Breast Oncol, Matsuyama, Ehime, Japan

[15] Iwate Med Univ, Dept Surg, Morioka, Iwate 020, Japan

[16] Nagoya City Univ Hosp, Dept Breast & Endocrine Surg, Nagoya, Aichi, Japan

[17] Hiroshima City Asa Hosp, Dept Surg, Hiroshima, Japan

[18] Higashi Municipal Hosp, Dept Surg, Nagoya, Aichi, Japan

[19] Kumamoto Univ Hosp, Dept Breast & Endocrine Surg, Kumamoto, Japan

[20] Kyoto Univ Hosp, Breast Surg Dept, Kyoto 606, Japan

来源：

BREAST CANCER RESEARCH AND TREATMENT | 2013年 / 142卷 / 01期

关键词：

Breast cancer; Neoadjuvant chemotherapy; Ki67; Capecitabine; Pathological complete response; Docetaxel; PATHOLOGICAL COMPLETE RESPONSE; SURGICAL ADJUVANT BREAST; DISEASE-FREE SURVIVAL; PHASE-III TRIAL; PLUS CYCLOPHOSPHAMIDE; MULTICENTER; THERAPY; LESIONS; B-27; P63;

D O I：

10.1007/s10549-013-2691-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This randomized, multicenter study compared the efficacy of docetaxel with or without capecitabine following fluorouracil/epirubicin/cyclophosphamide (FEC) therapy in operable breast cancer and investigated the role of Ki67 as a predictive biomarker. Patients were randomized to 4 cycles of docetaxel/capecitabine (docetaxel: 75 mg/m(2) on day 1; capecitabine: 1,650 mg/m(2) on days 1-14 every 3 weeks) or docetaxel alone (75 mg/m(2) on day 1 every 3 weeks) after completion of 4 cycles of FEC (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2) on day 1 every 3 weeks). The primary endpoint was the pathological complete response (pCR) rate. Predictive factor analysis was conducted using clinicopathological markers, including hormone receptors and Ki67 labeling index (Ki67LI). A total of 477 patients were randomized; the overall response in the docetaxel/capecitabine and docetaxel groups was 88.3 and 87.4 %, respectively. There were no significant differences in the pCR rate (docetaxel/capecitabine: 23 %; docetaxel: 24 %; p = 0.748), disease-free survival, or overall survival. However, patients with mid-range Ki67LI (10-20 %) showed a trend towards improved pCR rate with docetaxel/capecitabine compared to docetaxel alone. Furthermore, multivariate logistic regression analysis showed pre-treatment Ki67LI (odds ratio 1.031; 95 % CI 1.014-1.048; p = 0.0004) to be a significant predictor of pCR in this neoadjuvant treatment setting. Docetaxel/capecitabine (after 4 cycles of FEC) did not generate significant improvement in pCR compared to docetaxel alone. However, exploratory analyses suggested that assessment of pre-treatment Ki67LI may be a useful tool in the identification of responders to preoperative docetaxel/capecitabine in early-stage breast cancer.

引用

页码：69 / 80

页数：12

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