title: Neoadjuvant and adjuvant chemotherapy with doxorubicin and docetaxel in locally advanced breast cancer.
abstract: Fifty patients with histologically confirmed stage III breast cancer were enrolled in this study of doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 intravenously infused over 1 hour every 21 days with granulocyte colony-stimulating factor for 4 cycles. This was followed by surgery (mastectomy or lumpectomy) and 4 more cycles of doxorubicin/docetaxel postoperatively, then radiation and tamoxifen as indicated. Forty-six of the 50 patients (92%) completed neoadjuvant chemotherapy, and 38 patients (76%) completed adjuvant chemotherapy. Clinical response (defined as > 50% decrease in size of tumor) was achieved after 2 cycles in 37 patients (74%) and after 4 cycles in 42 of the 46 patients (91%) who finished neoadjuvant chemotherapy. Pathologic complete response (pCR; no pathologic invasive cancer) at the primary site was obtained in 7 of 46 patients (15%); 11 had no residual gross disease but did have microscopic persistence or microscopic complete response (mCR), for a combined pCR and mCR of 18 of 46 patients (39%). No treatment-related deaths occurred, but 3 patients died during treatment: 1 from progressive disease, 1 from a gastrointestinal bleeding, and 1 from unexplained sudden cardiac death. Dose-limiting toxicities were hematologic (grade 3 neutropenia in 5 patients and grade 4 in 23 patients). Congestive heart failure developed in 4 of 50 patients (8%), with a mean decrease in left ventricular ejection fraction (LVEF) of 20% in affected patients and 1 asymptomatic decrease in LVEF of 25%. At last follow-up, 10 patients had died of progressive disease, and 1 each from sudden cardiac death and lower gastrointestinal bleeding. In locally advanced breast cancer, neoadjuvant doxorubicin/docetaxel is a very active regimen that achieved pCR of 15% and a combined pCR and mCR of 39%, for an overall clinical response rate of 91%. Adjuvant chemotherapy was complicated by dropouts and congestive heart failure. This regimen should be used with close monitoring of cardiac function.
authors.affiliation: Division of Hematology/Medical Oncology, Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65203, USA. malhotrav@earthlink.net
authors.forename: Vikas
authors.initials: V
authors.lastname: Malhotra
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Dorr
authors.forename: Alan P
authors.initials: AP
authors.lastname: Lyss
authors.forename: Clay M
authors.initials: CM
authors.lastname: Anderson
authors.forename: Steven
authors.initials: S
authors.lastname: Westgate
authors.forename: Michelle
authors.initials: M
authors.lastname: Reynolds
authors.forename: Barbara
authors.initials: B
authors.lastname: Barrett
authors.forename: Michael C
authors.initials: MC
authors.lastname: Perry
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009417:Nerve Tissue / Q000187:drug effects; D009503:Neutropenia / Q000139:chemically induced; D011859:Radiography; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin