Gemcitabine, epirubicin, and paclitaxel versus fluorouracil, epirubicin, and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: a Central European Cooperative Oncology Group International, multicenter, prospective, randomized phase III trial.
BACKGROUND
The objectives of this phase III trial were to compare the time to progressive disease (TtPD), overall response rate (ORR), overall survival, and toxicity of gemcitabine, epirubicin, and paclitaxel (GET) versus fluorouracil (FU), epirubicin, and cyclophosphamide (FEC) as first-line therapy in patients with metastatic breast cancer (MBC).


METHODS
Female patients aged 18 to 75 years with stage IV and measurable MBC were enrolled and randomly assigned to either gemcitabine (1,000 mg/m(2), days 1 and 4), epirubicin (90 mg/m(2), day 1), and paclitaxel (175 mg/m(2), day 1) or FU (500 mg/m(2), day 1), epirubicin (90 mg/m(2), day 1), and cyclophosphamide (500 mg/m(2), day 1). Both regimens were administered every 21 days for a maximum of eight cycles.


RESULTS
Between October 1999 and November 2002, 259 patients (GET, n = 124; FEC, n = 135) were enrolled. Baseline characteristics were well balanced across treatment arms. After a median of 20.4 months of follow-up, median TtPD was 9.1 months and 9.0 months in the GET and FEC arms, respectively (P = .557). The ORR was 62.3% in the GET arm (n = 114) and 51.2% in the FEC arm (n = 129; P = .093). Grade 3 and 4 toxicities, including neutropenia, thrombocytopenia, anemia, stomatitis, neurosensory toxicity, and allergy, occurred significantly more often in the GET arm.


CONCLUSIONS
No significant differences in terms of TtPD and ORR were observed between the two treatment arms. Treatment-related toxicity was higher in the GET arm.
Zielinski
Christoph
C
Department of Medicine I, University Hospital, 18-20 Waehringer Guertel, A-1090 Vienna, Austria. christoph.zielinski@meduniwien.ac.at
Beslija
Semir
S
Mrsic-Krmpotic
Zrinka
Z
Welnicka-Jaskiewicz
Marzena
M
Wiltschke
Christoph
C
Kahan
Zsuzsanna
Z
Grgic
Mislav
M
Tzekova
Valentina
V
Inbar
Moshe
M
Cervek
Jozika
J
Chernozemsky
Ivan
I
Szanto
Janos
J
Spanik
Stanislav
S
Wagnerova
Maria
M
Ghilezan
Nicolae
N
Pawlega
Janusz
J
Vrbanec
Damir
D
Khamtsov
Dmitry
D
Soldatenkova
Victoria
V
Brodowicz
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003520:Cyclophosphamide / Q000627:therapeutic use* / Q000633:toxicity; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use* / Q000633:toxicity; D015251:Epirubicin / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D043823:Taxoids / Q000627:therapeutic use* / Q000633:toxicity
D043823:Taxoids; D003841:Deoxycytidine; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil