Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.
OBJECTIVE
We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy.


METHODS
A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups.


RESULTS
Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001).


CONCLUSIONS
Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.
Tominaga
Takeshi
T
Breast Cancer Center, Toyosu Hospital, Showa University School of Medicine, Tokyo, Japan. t-tominaga@hkg.odn.ne.jp
Koyama
Hiroki
H
Toge
Tetsuya
T
Miura
Shigeto
S
Sugimachi
Keizo
K
Yamaguchi
Susumu
S
Hirata
Koichi
K
Monden
Yasumasa
Y
Nomura
Yasuo
Y
Toi
Masakazu
M
Kimijima
Izo
I
Noguchi
Shinzaburo
S
Sonoo
Hiroshi
H
Asaishi
Kazuaki
K
Ikeda
Tadashi
T
Morimoto
Tadaoki
T
Ota
Jun
J
Ohashi
Yasuo
Y
Abe
Osahiko
O
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007564:Japan; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D003520:Cyclophosphamide; C025034:doxifluridine