Epirubicin-cyclophosphamide adjuvant chemotherapy plus tamoxifen administered concurrently versus sequentially: randomized phase III trial in postmenopausal node-positive breast cancer patients. A GEICAM 9401 study.
BACKGROUND
A prospective randomized clinical trial was implemented to assess whether the concomitant or the sequential addition of tamoxifen to chemotherapy provides improved clinical benefit in the adjuvant treatment of breast cancer in postmenopausal patients.


METHODS
Four-hundred and eighty-five patients with node-positive operable disease were randomized to receive tamoxifen (20 mg/day) concomitantly (CON) or sequentially (SEQ) to EC chemotherapy (epirubicin 75 mg/m(2) + cyclophosphamide 600 mg/m(2) on day 1, every 21 days for four cycles).


RESULTS
In the 474 fully evaluable patients there were 96 events; eight being second neoplasms and 88 being related to the breast cancer. Of these, 48 of 88 occurred in the CON arm and 40 of 88 in the SEQ arm. The Kaplan-Meier estimation of disease-free survival (DFS) at 5 years was 70% in the CON and 75% in the SEQ group (log-rank test, P = 0.43). Adjusted hazard ratio for treatment was 1.11 (95% confidence interval 0.71-1.73; P = 0.64).


CONCLUSIONS
This study fails to show an advantage of one treatment arm over the other, but a trend, albeit non-significant, appears to favor the sequential addition of tamoxifen to epirubicin + cyclophosphamide and, as such, warrants further investigation.
Pico
C
C
Servicio de Oncología Médica, Hospital General Universitario de Alicante, Alicante, Spain.
Martin
M
M
Jara
C
C
Barnadas
A
A
Pelegri
A
A
Balil
A
A
Camps
C
C
Frau
A
A
Rodriguez-Lescure
A
A
Lopez-Vega
J M
JM
De La Haba
J
J
Tres
A
A
Alvarez
I
I
Alba
E
E
Arcusa
A
A
Oltra
A
A
Batista
N
N
Checa
T
T
Perez-Carrion
R
R
Curto
J
J
D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004347:Drug Interactions; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017698:Postmenopause; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D015251:Epirubicin; D003520:Cyclophosphamide