Adjuvant chemotherapy in older women with early-stage breast cancer.
BACKGROUND
Older women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older.


METHODS
We randomly assigned patients with stage I, II, IIIA, or IIIB breast cancer to standard chemotherapy (either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide plus doxorubicin) or capecitabine. Endocrine therapy was recommended after chemotherapy in patients with hormone-receptor-positive tumors. A Bayesian statistical design was used with a range in sample size from 600 to 1800 patients. The primary end point was relapse-free survival.


RESULTS
When the 600th patient was enrolled, the probability that, with longer follow-up, capecitabine therapy was highly likely to be inferior to standard chemotherapy met a prescribed level, and enrollment was discontinued. After an additional year of follow-up, the hazard ratio for disease recurrence or death in the capecitabine group was 2.09 (95% confidence interval, 1.38 to 3.17; P<0.001). Patients who were randomly assigned to capecitabine were twice as likely to have a relapse and almost twice as likely to die as patients who were randomly assigned to standard chemotherapy (P=0.02). At 3 years, the rate of relapse-free survival was 68% in the capecitabine group versus 85% in the standard-chemotherapy group, and the overall survival rate was 86% versus 91%. Two patients in the capecitabine group died of treatment-related complications; as compared with patients receiving capecitabine, twice as many patients receiving standard chemotherapy had moderate-to-severe toxic effects (64% vs. 33%).


CONCLUSIONS
Standard adjuvant chemotherapy is superior to capecitabine in patients with early-stage breast cancer who are 65 years of age or older. (ClinicalTrials.gov number, NCT00024102.)
University of Vermont, Burlington, USA. muss@gmail.com
Hyman B
HB
Muss
Donald A
DA
Berry
Constance T
CT
Cirrincione
Maria
M
Theodoulou
Ann M
AM
Mauer
Alice B
AB
Kornblith
Ann H
AH
Partridge
Lynn G
LG
Dressler
Harvey J
HJ
Cohen
Heather P
HP
Becker
Patricia A
PA
Kartcheske
Judith D
JD
Wheeler
Edith A
EA
Perez
Antonio C
AC
Wolff
Julie R
JR
Gralow
Harold J
HJ
Burstein
Ahmad A
AA
Mahmood
Gustav
G
Magrinat
Gutav
G
Magrinat
Barbara A
BA
Parker
Ronald D
RD
Hart
Debjani
D
Grenier
Larry
L
Norton
Clifford A
CA
Hudis
Eric P
EP
Winer
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / 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; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011960:Receptors, Estrogen / Q000032:analysis; D016019:Survival Analysis
D000964:Antimetabolites, Antineoplastic; D011960:Receptors, Estrogen; D003841:Deoxycytidine; D000069287:Capecitabine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate