Phase III multicenter trial of doxorubicin plus cyclophosphamide followed by paclitaxel compared with doxorubicin plus paclitaxel followed by weekly paclitaxel as adjuvant therapy for women with high-risk breast cancer.
OBJECTIVE
This study compared disease-free survival (DFS) obtained with two different regimens of adjuvant therapy in high-risk breast cancer.


METHODS
Women (who had performance status [PS] of 0 to 1) with operable, histologically confirmed, stage I to III adenocarcinoma of the breast were eligible. Patients had undergone primary surgery with no residual tumor. Treatments were as follows: arm 1 was doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 3 weeks for four cycles followed by paclitaxel 175 mg/m(2) every 3 weeks for four cycles (ie, AC-P); and arm 2 was doxorubicin 50 mg/m(2) plus paclitaxel 200 mg/m(2) every 3 weeks for four cycles followed by paclitaxel 80 mg/m(2) weekly for 12 weeks.


RESULTS
Overall, 1,830 patients were enrolled and 1,801 were treated: arm 1 (n = 906; AC-->P) and arm 2 (n = 895; AP-WP). Overall, patients had a PS of 0 (88%), had estrogen receptor and progesterone receptor-positive disease (52%), had one to three positive nodes (46%), and were postmenopausal (57%); the median age was 52 years. Currently, 1,640 patients (90%) are alive. The 6-year DFS was 79% to 80% in both groups. Disease relapse was the cause of death for 83 patients in arm 1 and in 66 patients of arm 2. Overall 6-year survival rates were 82% and 87% in arms 1 and 2, respectively. Reasons for patients being taken off study treatment included toxicity (13% in arm 1 v 20% in arm 2), progressive disease or recurrence (7% v 5%), and consent withdrawn (9% v 8%), respectively. The most frequent toxicities were hematologic, including neutropenia and leukopenia followed by neuropathy, myalgia, nausea, fatigue, headache, arthralgia, and vomiting.


CONCLUSIONS
The results indicate that the AP-WP regimen is an equally effective and tolerable option for the adjuvant treatment of patients with high-risk breast cancer. The substitution of paclitaxel for cyclophosphamide results in comparable effectiveness of the regimen.
Loesch
David
D
US Oncology Research, The Woodlands, TX, USA. dloesch@carismpi.com
Greco
F Anthony
FA
Senzer
Neil N
NN
Burris
Howard A
HA
Hainsworth
John D
JD
Jones
Stephen
S
Vukelja
Svetislava J
SJ
Sandbach
John
J
Holmes
Frankie
F
Sedlacek
Scot
S
Pippen
John
J
Lindquist
Deborah
D
McIntyre
Kristi
K
Blum
Joanne L
JL
Modiano
Manuel R
MR
Boehm
Kristi A
KA
Zhan
Feng
F
Asmar
Lina
L
Robert
Nicholas
N
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel