A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up.
BACKGROUND
The current study was performed to assess whether sequential potentially noncross-resistant chemotherapy prolongs disease-free survival (DFS) and overall survival (OS) in patients with operable breast carcinoma.


METHODS
Seven hundred eighty-nine patients were registered and followed for a median of 10 years. They were treated in two groups. In Group 1, patients age < 50 years or age > 50 years but with either negative or unknown estrogen receptor (ER) status were randomized to receive 6 cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) alone or followed by 4 cycles of methotrexate and vinblastine (MV). In Group 2, patients age > or = 50 years with ER-positive disease were randomized to receive either tamoxifen or combination chemotherapy (FAC + MV) for 10 cycles. Analysis was performed according to allocated treatment (intention to treat), with all randomized patients included.


RESULTS
In Group 1 there were no significant differences with regard to DFS or OS between the two treatment arms. The DFS at 5 years was 0.70 and 0.76, respectively, for FAC compared with FAC+MV (P = 0.26). The OS was similar for both groups (0.84 vs. 0.83). It is interesting to note that there was a statistically nonsignificant trend for improved DFS in the FAC + MV arm for patients who were ER-positive. In Group 2, tamoxifen alone led to more prolonged DFS compared to FAC+MV (0.78 vs. 0.66, respectively) but this did not reach statistical significance (P = 0.28). OS also was associated with a trend (P = 0.86) toward prolonged survival for the tamoxifen arm compared with the FAC+MV arm (0.85 vs. 0.74, respectively).


CONCLUSIONS
The results of the current trial concerning sequential adjuvant chemotherapy for operable breast carcinoma, which to our knowledge contains the longest follow-up presented to date, failed to demonstrate any additional benefit from the addition of 4 cycles of MV to 6 cycles of FAC chemotherapy.
Assikis
Vasily
V
Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Buzdar
Aman
A
Yang
Ying
Y
Smith
Terry
T
Theriault
Richard
R
Booser
Daniel
D
Valero
Vicente
V
Walters
Ronald
R
Singletary
Eva
E
Ames
Frederick
F
Hortobagyi
Gabriel
G
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D011960:Receptors, Estrogen; D013629:Tamoxifen; D014747:Vinblastine; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate