title: A pilot study of dose intense doxorubicin and cyclophosphamide followed by infusional paclitaxel in high-risk primary breast cancer.
abstract: We conducted a pilot study of dose dense doxorubicin and cyclophosphamide (AC) combination chemotherapy followed by infusional paclitaxel (T) in primary breast cancer to determine its safety and feasibility. Twenty-two subjects (10 with stage II and > or = 4 positive lymph nodes, and 12 with stage III disease) were treated with AC (A 60 mg/m2 and C 2000 mg/m2) with filgrastim every 14 days for three cycles followed by infusional paclitaxel (140 mg/m2 over 96 h) every 14 days for three cycles. Mean overall cycle length was 15.3 days and mean duration of therapy was 92 days. Dose reductions of C or T were required in 7/132 (5.3%) cycles for mucositis, diarrhea, or failure to recover platelets by day 15. Ninety-five percent of subjects had grade 4 neutropenia and 1 subject had a platelet nadir of < 20,000. Actual delivered dose intensity (DI) over six cycles was: A 27 mg/m2 per week; C 892 mg/m2 per week; T 64 mg/m2 per week (90.6, 89.2, and 91.4% of planned DI, respectively). Average total dose administered was: A 180 mg/m2; C 5880 mg/m2; T 403 mg/m2 (100, 98, and 96% of planned total doses, respectively). Clinical response rate in 10 subjects receiving neoadjuvant therapy was 100% (4 complete response, 6 partial response). Four subjects had a pathologic complete response (three subjects without evidence of malignancy and one subject with ductal carcinoma in situ.) Administration of dose dense AC followed by infusional paclitaxel in 14-day cycles is feasible and this regimen is active in breast cancer.
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. zujewskj@mail.nih.gov
authors.forename: Jo Anne
authors.initials: JA
authors.lastname: Zujewski
authors.forename: Jennifer
authors.initials: J
authors.lastname: Eng-Wong
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Catherine
authors.initials: C
authors.lastname: Chow
authors.forename: David
authors.initials: D
authors.lastname: Danforth
authors.forename: David R
authors.initials: DR
authors.lastname: Kohler
authors.forename: Georgia
authors.initials: G
authors.lastname: Cusack
authors.forename: David
authors.initials: D
authors.lastname: Riseberg
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Cowan
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel