Phase II study of gefitinib in combination with docetaxel as first-line therapy in metastatic breast cancer

被引:72
作者
Ciardiello, F.
Troiani, T.
Caputo, F.
De Laurentiis, M.
Tortora, G.
Palmieri, G.
De Vita, F.
Diadema, M. R.
Orditura, M.
Colantuoni, G.
Gridelli, C.
Catalano, G.
De Placido, S.
Bianco, A. R.
机构
[1] Univ Naples 2, Cattedra Oncol Med, Dipartimento Medicochirurg Internist Clin & Speri, I-80131 Naples, Italy
[2] Univ Naples 2, Cattedra Oncol Med, Dipartimento Endocrinol & Oncol Mol & Clin, I-80131 Naples, Italy
[3] Osped SG Moscati, Div Med Oncol, Avellino, Italy
关键词
metastatic breast cancer; taxanes; small-molecule EGFR tyrosine kinase inhibitors; combination therapy;
D O I
10.1038/sj.bjc.6603141
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have evaluated the activity and safety of gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with docetaxel as first-line treatment of women with metastatic breast cancer (MBC). In total, 41 patients with MBC were enrolled in a first-line combination therapy study with oral gefitinib (250 mg day(-1)) and intravenous docetaxel (75 mg m(-2), the first 14 patients; or 100 mg m(-2), the following 27 patients, on day 1 of a 3-week cycle). Out of 41 patients, 38 received at least one cycle of therapy. There were no differences in activity or tolerability between the two docetaxel doses. G3/4 toxicities were neutropenia (49%), diarrhoea (10%), acne-like rash (5%), and anaemia (2%). Complete plus partial responses (CR+PR) were observed in 22 out of 41 patients with a 54% response rate (95% confidence interval (CI) 45 - 75%). The 22 patients that achieved a response following six cycles of docetaxel plus gefitinib continued gefitinib monotherapy ( median duration, 24 weeks; range, 2 - 108+ weeks). Two patients with PR following combination therapy achieved a CR during gefitinib monotherapy. Complete plus partial responses correlated with oestrogen receptor ( ER) status, since they occurred in 19 out of 27 (70%) patients with ER-positive tumours as compared to three out of 14 (21%) patients with ER-negative tumours (P=0.01).
引用
收藏
页码:1604 / 1609
页数:6
相关论文
共 44 条
[11]   ONE-SAMPLE MULTIPLE TESTING PROCEDURE FOR PHASE-II CLINICAL-TRIALS [J].
FLEMING, TR .
BIOMETRICS, 1982, 38 (01) :143-151
[12]   THE EPIDERMAL GROWTH-FACTOR RECEPTOR AS A PROGNOSTIC MARKER - RESULTS OF 370 PATIENTS AND REVIEW OF 3009 PATIENTS [J].
FOX, SB ;
SMITH, K ;
HOLLYER, J ;
GREENALL, M ;
HASTRICH, D ;
HARRIS, AL .
BREAST CANCER RESEARCH AND TREATMENT, 1994, 29 (01) :41-49
[13]   Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer [J].
Greenberg, PAC ;
Hortobagyi, GN ;
Smith, TL ;
Ziegler, LD ;
Frye, DK ;
Buzdar, AU .
JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (08) :2197-2205
[14]   Developing inhibitors of the epidermal growth factor receptor for cancer treatment [J].
Grünwald, V ;
Hidalgo, M .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (12) :851-867
[15]   Timeline - Gefitinib - a novel targeted approach to treating cancer [J].
Herbst, RS ;
Fukuoka, M ;
Baselga, J .
NATURE REVIEWS CANCER, 2004, 4 (12) :956-965
[16]   Can we cure limited metastatic breast cancer? [J].
Hortobagyi, GN .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (03) :620-623
[17]   NONPARAMETRIC-ESTIMATION FROM INCOMPLETE OBSERVATIONS [J].
KAPLAN, EL ;
MEIER, P .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1958, 53 (282) :457-481
[18]   THE PROGNOSTIC VALUE OF EPIDERMAL GROWTH-FACTOR RECEPTOR (EGF-R) IN PRIMARY BREAST-CANCER - RESULTS OF A 10-YEAR FOLLOW-UP-STUDY [J].
KLIJN, JGM ;
LOOK, MP ;
PORTENGEN, H ;
ALEXIEVAFIGUSCH, J ;
VANPUTTEN, WLJ ;
FOEKENS, JA .
BREAST CANCER RESEARCH AND TREATMENT, 1994, 29 (01) :73-83
[19]   THE CLINICAL-SIGNIFICANCE OF EPIDERMAL GROWTH-FACTOR RECEPTOR (EGF-R) IN HUMAN BREAST-CANCER - A REVIEW ON 5232 PATIENTS [J].
KLIJN, JGM ;
BERNS, PMJJ ;
SCHMITZ, PIM ;
FOEKENS, JA .
ENDOCRINE REVIEWS, 1992, 13 (01) :3-17
[20]   Elevated levels of epidermal growth factor receptor/c-erbB2 heterodimers mediate an autocrine growth regulatory pathway in tamoxifen-resistant MCF-7 cells [J].
Knowlden, JM ;
Hutcheson, IR ;
Jones, HE ;
Madden, T ;
Gee, JMW ;
Harper, ME ;
Barrow, D ;
Wakeling, AE ;
Nicholson, RI .
ENDOCRINOLOGY, 2003, 144 (03) :1032-1044