Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5‐fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma

• Published in: Cancer 2000-12, Vol.89 (12), p.2521-2526
• Main Authors: Bang, Soo‐Mee, Heo, Dae Seog, Lee, Ki Hyeong, Byun, Jae Ho, Chang, Heung Moon, Noh, Dong‐Yong, Choe, Kuk Jin, Bang, Yung‐Jue, Kim, Sung Rok, Kim, Noe Kyeong
• Format: Article
• Language: English
• Subjects: adjuvant chemotherapy; Adult; and 5‐fluorouracil (CMF); Anemia - chemically induced; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; breast neoplasm; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Breast Neoplasms - radiotherapy; Chemotherapy, Adjuvant; Combined Modality Therapy; cyclophosphamide; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Dose-Response Relationship, Drug; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; doxorubicin and cyclophosphamide (AC); Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Follow-Up Studies; Humans; Leukopenia - chemically induced; Lymph Nodes - drug effects; Lymph Nodes - pathology; Lymph Nodes - radiation effects; methotrexate; Methotrexate - administration & dosage; Methotrexate - adverse effects; Middle Aged; Neoplasm Recurrence, Local - prevention & control; Neoplasm Staging; Premenopause; Survival Analysis; Time Factors; Treatment Outcome
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/1097-0142(20001215)89:12<2521::AID-CNCR2>3.0.CO;2-F

BACKGROUND This randomized controlled trial was to determine whether a combination chemotherapy regimen that contains anthracycline (doxorubicin and cyclophosphamide [AC]) is superior to the conventional cyclophosphamide, methotrexate, and 5‐fluorouracil [CMF] combination in premenopausal women with axillary lymph node positive Stage II breast carcinoma. METHODS Premenopausal women with lymph node positive breast carcinoma were stratified according to age (younger than 35 or 35 years or older) and the number of positive axillary lymph nodes (1–3, 4–9, or ≥ 10) and then randomly assigned to receive either doxorubicin 40 mg/m2 and cyclophosphamide 600 mg/m2 intravenously (i.v.) every 3 weeks or cyclophosphamide 100 mg/m2 orally on Days 1 through 14, methotrexate 40 mg/m2 and 5‐fluorouracil 500 mg/m2 i.v. on Days 1 and 8 every 4 weeks. Both arms were scheduled for six cycles. RESULTS The median follow‐up was 57 months. Eighteen of the 55 AC patients developed recurrence compared with 16 of the 69 CMF patients. The corresponding 5‐year recurrence free survival rates were 64% and 78%, respectively (P = 0.12). The site of the first recurrence for AC patients was locoregional in 7%, distant in 22%, and combined in 4%. The corresponding data for the CMF arm were 4%, 16%, and 3%, respectively. Six AC patients died compared with 9 CMF patients. The corresponding 5‐year survival rates were 90% and 86%, respectively (P = 0.96). More leukopenia (52%, mostly Grade 1–2) occurred in the CMF arm than in the AC arm (33%, P = 0.001), but no febrile episode was accompanied with leukopenia. CONCLUSIONS This study showed no difference between AC and CMF with respect to both disease free and overall survival rates in premenopausal women with axillary lymph node positive breast carcinoma. Cancer 2000;89:2521–6. © 2000 American Cancer Society. In this randomized controlled trial, adjuvant doxorubicin and cyclophosphamide chemotherapy showed no survival benefit compared with conventional cyclophosphamide, methotrexate, and 5‐fluorouracil in premenopausal women with axillary lymph node positive breast carcinoma.