Randomized, controlled, multicenter phase III trial of standard-dose fluorouracil-epirubicin-cyclophosphamide (FEC), compared with time-intensive FEC (FEC-G) and mitoxantrone-methotrexate-mitomycin C (MMM-G) in metastatic breast carcinoma

被引:13
作者
Capotorto, AM
Pavesi, L
Pedrazzoli, P
Da Prada, GA
Zamagni, C
Massidda, B
Farris, A
Martoni, A
Lelli, G
Della Cuna, GR
机构
[1] Fdn S Maugeri, Div Med Oncol, IRCCS, I-27100 Pavia, Italy
[2] Osped Casa Sollievo Sofferenza, IRCCS, Div Oncol, San Giovanni Rotondo, Italy
[3] AO S Orsola Malpighi, Div Med Oncol, Bologna, Italy
[4] Univ Cagliari, Cattedra Oncol Med, Cagliari, Italy
[5] Univ Sassari, Cattedra Oncol Med, I-07100 Sassari, Italy
关键词
dose-intensity; time-intensification; breast cancer; FEC regimen; MMM regimen; metastatic breast cancer;
D O I
10.1179/joc.2003.15.2.184
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The purpose of this multicenter phase III trial was to assess the impact of a time-intensification of FEC (fluorouracil, epirubicin, cyclophosphamide) and MMM (mitoxantrone, methotrexate, mitomycin C) regimens, supported by lenograstim (G-CSF) on the objective response rate, time to progression and survival of patients with chemotherapy-naive metastatic breast cancer (mbc). Women with mbc were randomized to receive as first-line chemotherapy either standard-dose FEC (all doses in mg/m(2)): arm A (500, 75, 500 every 21 days), or time-intensified FEC-G: arm B (500, 75, 500 every 14 days), or time-intensified MMM-G: arm C (mitoxantrone 10, methotrexate 35 every 14 days and mitomycin C 10 every 28 days), both with support of lenograstim (G-CSF 150 mug/m(2)/day sc for 10 days). All study treatments were administered for six cycles. Eligible female patients were in the 3170 year range with histologically proven mbc, and measurable or evaluable disease. An intent-to-treat analysis was performed. The overall response rate (CR + PR, intent-to-treat analysis) was significantly improved in the time-intensified FEC-G regimen (69%) in comparison with standard-dose FEC (41%), p=0.002. Time-intensified MMM-G (51%) did not lead to a significant improvement in the response rate. The percentage of complete responses was significantly higher in the FEC-G arm as compared to standard-dose FEC (17% vs. 4.7%; p=0.002). The median duration was longer in the intensified-dose arms without, however, achieving a statistically significant improvement. The median time to progression (TTP), and the median survival time did not differ between the three treatment arms. Grade 3-4 leukopenia was significantly higher (p<0.001) in the standard FEC regimen-treated patients. Thrombocytopenia was significantly higher (p<0.001) in both intensified regimens. Alopecia and mucositis were significantly more frequent in both anthracycline-containing regimens (p=0.003). Other hematological and non hematological toxicities were similar in the 3 treatment arms. The increase of dose-intensity of both FEC and MMM regimens improved activity, but not efficacy as compared to standard FEC regimen in our group of chemotherapy-naive, metastatic breast cancer patients.
引用
收藏
页码:184 / 191
页数:8
相关论文
共 30 条
[1]  
Agresti A., 1990, Analysis of categorical data
[2]   Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: A randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group [J].
Bastholt, L ;
Dalmark, M ;
Gjedde, SB ;
Pfeiffer, P ;
Pedersen, D ;
Sandberg, E ;
Kjaer, M ;
Mouridsen, HT ;
Rose, C ;
Nielsen, OS ;
Jakobsen, P ;
Bentzen, SM .
JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (04) :1146-1155
[3]   The bigger the better? ... or what we know and what we still need to learn about anthracycline dose per course, dose density and cumulative dose in the treatment of breast cancer [J].
Biganzoli, L ;
Piccart, MJ .
ANNALS OF ONCOLOGY, 1997, 8 (12) :1177-1182
[4]  
BONNETERRE J, 1991, J CLIN ONCOL, V9, P305
[5]   Doubling epirubicin dose intensity (100 mg/m(2) versus 50 mg/m(2)) in the FEC regimen significantly increases response rates. An international randomised phase III study in metastatic breast cancer [J].
Brufman, G ;
Colajori, E ;
Ghilezan, N ;
Lassus, M ;
Martoni, A ;
Perevodchikova, N ;
Tosello, C ;
Viaro, D ;
Zielinski, C ;
Krainer, M ;
Salzer, H ;
Schuller, J ;
Dittrich, C ;
Scheithauer, W ;
Zamagni, C ;
Ambrosini, G ;
Colucci, G ;
Gentilini, P ;
Zaniboni, A ;
Pacini, P ;
Bianco, R ;
Mustacchi, G ;
DAprile, M ;
DeMatteis, A ;
Oliveira, C ;
Jordaan, J ;
Gudgeon, A ;
VanZyl, J ;
Rakowsky, E ;
Inbar, M ;
Rath, P ;
Cohen, Y ;
Shani, A ;
Fried, G ;
Hegg, R ;
Neto, AB ;
Bader, G ;
Braga, RF ;
Vitoc, C ;
Puerto, VML ;
Valle, AE ;
Salazar, JD ;
Sanchez, JC ;
Villela, GM ;
Fountzilas, G .
ANNALS OF ONCOLOGY, 1997, 8 (02) :155-162
[6]   A COMPARISON OF 2 DOSES OF ADRIAMYCIN IN THE PRIMARY CHEMOTHERAPY OF DISSEMINATED BREAST-CARCINOMA [J].
CARMOPEREIRA, J ;
COSTA, FO ;
HENRIQUES, E ;
GODINHO, F ;
CANTINHOLOPES, MG ;
SALESLUIS, A ;
RUBENS, RD .
BRITISH JOURNAL OF CANCER, 1987, 56 (04) :471-473
[7]  
COX DR, 1972, J R STAT SOC B, V34, P187
[8]   Accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with standard CEF in metastatic breast cancer patients: Results of a multicenter, randomized phase III study of the Italian Gruppo Oncologico Nord-Ouest-Mammella Inter Gruppo Group [J].
Del Mastro, L ;
Venturini, M ;
Lionetto, R ;
Carnino, F ;
Guarneri, D ;
Gallo, L ;
Contu, A ;
Pronzato, P ;
Vesentini, L ;
Bergaglio, M ;
Comis, S ;
Rosso, R .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (08) :2213-2221
[9]  
DIXON WJ, 1992, BMDP BIOMEDICAL COMP
[10]   Lenograstim - An update of its pharmacological properties and use in chemotherapy-induced neutropenia and related clinical settings [J].
Dunn, CJ ;
Goa, KL .
DRUGS, 2000, 59 (03) :681-717