Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer.
OBJECTIVE
The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant chemotherapy regimen. Studies of docetaxel and cyclophosphamide (TC) in metastatic breast cancer (MBC) showed promise in MBC. In 1997, we initiated a randomized adjuvant trial of TC compared with standard-dose AC with a primary end point of disease-free survival (DFS).


METHODS
Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor. Between June 1997 and December 1999, 1,016 patients were randomly assigned to four cycles of either standard-dose AC (60 and 600 mg/m2, respectively; n = 510) or TC (75 and 600 mg/m2, respectively; n = 506), administered intravenously every 3 weeks as adjuvant chemotherapy. Radiation therapy (as indicated) and tamoxifen, for patients with hormone receptor-positive disease, were administered after completion of chemotherapy.


RESULTS
Both treatment groups (TC and AC) were well balanced with respect to major prognostic factors. Patients were observed through 2005 for a median of 5.5 years. At 5 years, DFS rate was significantly superior for TC compared with AC (86% v 80%, respectively; hazard ratio [HR] = 0.67; 95% CI, 0.50 to 0.94; P = .015). Overall survival rates for TC and AC were 90% and 87%, respectively (HR = 0.76; 95% CI, 0.52 to 1.1; P = .13). More myalgia, arthralgia, edema, and febrile neutropenia occurred on the TC arm; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure.


CONCLUSIONS
At 5 years, TC was associated with a superior DFS and a different toxicity profile compared with AC.
Jones
Stephen E
SE
US Oncology Research, Inc, Texas Oncology, Dallas, TX 75246, USA. steve.jones@usoncology.com
Savin
Michael A
MA
Holmes
Frankie Ann
FA
O'Shaughnessy
Joyce A
JA
Blum
Joanne L
JL
Vukelja
Svetislava
S
McIntyre
Kristi J
KJ
Pippen
John E
JE
Bordelon
James H
JH
Kirby
Robert
R
Sandbach
John
J
Hyman
William J
WJ
Khandelwal
Pankaj
P
Negron
Angel G
AG
Richards
Donald A
DA
Anthony
Stephen P
SP
Mennel
Robert G
RG
Boehm
Kristi A
KA
Meyer
Walter G
WG
Asmar
Lina
L
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D011446:Prospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D014839:Vomiting / Q000139:chemically induced
D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide