Randomized trial of cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil with node-positive breast cancer in Japan.
BACKGROUND
To compare the cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy and the anthracycline-containing regimen cyclophosphamide, epirubicin, and fluorouracil (CEF) to evaluate the efficacy and safety of the latter.


METHODS
A total of 294 patients with axillary node-positive primary breast cancer of STAGE I-IIIa were randomly assigned to either CEF [cyclophosphamide (CPA) 500 mg/m(2) i.v. days 1 and 8; epirubicin (EPI) 60 mg/m(2) i.v. day 1; and 5-fluorouracil (5-FU) 500 mg/m(2) i.v. days 1 and 8] or CMF [CPA 500 mg/m(2) i.v. days 1 and 8; methotrexate (MTX) 40 mg/m(2) i.v. days 1 and 8; and 5-FU 500 mg/m(2) i.v. days 1 and 8]. Both treatment regimens were comprised of six cycles at 4-week intervals. Tamoxifen (TAM) 20 mg/day was concomitantly given to estrogen receptor (ER)-positive patients and those with undetermined ER status for 2 years.


RESULTS
The overall 5-year survival was 77.1% for CEF and 71.4% for CMF [p = 0.24; hazard ratio 0.79 (95% CI 0.50-1.24)], and the 5-year disease-free survival was 55.7% for CEF and 48.9% for CMF [p = 0.15; hazard ratio 0.80 (95% CI 0.57-1.12)]. Although the log-rank test did not show a significant difference, both overall and disease-free survivals were higher for CEF according to the point estimates. Adverse drug reactions (ADRs) occurred more frequently in CEF.


CONCLUSIONS
Whereas CEF had a good trend compare with CMF, it could not be proven statistically significant. The principal cause of the failure seems to be insufficient power, that is, the dose intensity (EPI: 60 mg/m(2)) set 10 years ago, when the trial began, was low, and the number of trial subjects was small because of the background of the times, which made the accumulation of cases extremely difficult. However, the trial should be considered to be meaningful, as it was the first, formally conducted controlled trial on chemotherapy in Japan.
Kimura
Morihiko
M
Department of Surgery, Gunma Prefectural Cancer Center, Ota, Japan. mkimura@qk9.so-net.ne.jp
Tominaga
Takeshi
T
Takatsuka
Yuichi
Y
Toi
Masakazu
M
Abe
Rikiya
R
Koyama
Hiroki
H
Takashima
Shigemitsu
S
Nomura
Yasuo
Y
Miura
Shigeto
S
Kimijima
Izo
I
Tashiro
Hideya
H
Ohashi
Yasuo
Y
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002293:Adenocarcinoma, Scirrhous / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007564:Japan; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D011960:Receptors, Estrogen; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate