Sixteen-Week Dose-Intense Chemotherapy in the Adjuvant Treatment of Breast Cancer

• Published in: JNCI : Journal of the National Cancer Institute 1990-04, Vol.82 (7), p.570-574
• Main Authors: Abeloff, Martin D., Beveridge, Roy A., Donehower, Ross C., Fetting, John H., Davidson, Nancy E., Gordon, Gary G., Waterfield, William C., Damron, Dorothy J.
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - therapy; Combined Modality Therapy; Cyclophosphamide - administration & dosage; Doxorubicin - administration & dosage; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Humans; Leucovorin - administration & dosage; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Pharmacology. Drug treatments; Pilot Projects; Vincristine - administration & dosage
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/82.7.570

Fifty-three women with breast cancer were treated with a new 16-week dose-intense, chemotherapy regimen. Patients with operable breast cancer with 10 or more histologically positive axillary nodes were treated with this five-drug regimen that incorporated the concepts of weekly chemotherapy, sequential administration of antimetabolites, and continuous infusion of fluorouracil (5-FU). The chemotherapy regimen consisted of eight cycles (each of 2 wk duration) of 100 mg of cyclophosphamide/m2 orally on days 1–7, 40 mg of doxorubicin/m2 intravenous (IV) on day 1, 100 mg of methotrexate/m2 IV on day 1 with 10 mg of leucovorin rescue/m2 every 6 hours for six oral doses on day 2, 1 mg of vincristine IV on day 1, and 600 mg of 5-FU/m2 IV at hour 20 over 2 hours. A continuous infusion of 300 mg of 5-FU/m2 per day was given IV on days 8–9 of each 2-week cycle. The doses and schedule of drug administration were designed to minimize dosage reduction and treatment delay. At a median follow-up of 17 months, there have been eight relapses in the 53 patients. The actuarial 3-year disease-free survival is 80% (95% confidence interval, 62% to 90%). The major side effects were attributable to myelosuppression. Absolute neutrophil counts less than 250/μL were noted in 12 (23%) patients; seven patients (13%) required hospitalization for management of neutropenic fever. No treatment-related deaths occurred. Ninetyfour percent of the planned doses were administered, and only 5% of the courses were delayed because of toxic reactions. The encouraging therapeutic data, manageable side effects, and our ability to deliver over 90% of the planned doses provide the rationale for a phase III comparison of this new dose-intense regimen and standard chemotherapy in patients with operable disease and positive axillary nodes. [J Natl Cancer Inst 82: 570–574, 1990]