title: Phase II study of dose-dense sequential doxorubicin and docetaxel for patients with advanced operable and inoperable breast cancer.
abstract: Rapid sequential delivery of doxorubicin 75 mg/m2 q 2 weeksx3 cycles followed by docetaxel 100 mg/m2 q 2 weeksx3 cycles, with filgrastim support was evaluated in patients with inoperable and large operable breast cancers who were not initially candidates for breast conservation therapy. Postoperative CMF chemotherapy and/or radiation were administered based on surgical findings. Median age of the 39 enrolled patients was 47 (range 27-59), stage IIA (6 patients), IIB (14 patients), IIIA (10 patients), IIIB (9 patients), and 23 patients (59%) had clinical nodal involvement. The average bidimensional tumor size before treatment was 30 cm2. Clinical responses included 13 (33%) complete responses, 23 (59%) partial responses, 1 stable disease, and 2 progressive disease, for an overall response rate of 92%. Clinical response rate was 11/13(85%) in HER2/neu positive patients compared to 25/26 (96%) in tumors that did not express HER2/neu. Twenty patients (51%) underwent breast conservation surgery. Pathologic tumor response at the time of definitive surgery included 4 pathologic CR (pCR, 10%), 4 microscopic invasion (pINV), and 14 (36%) pathologically negative axillary nodes. pCR was not observed in any HER2/neu positive patients. 5/39 patients were unable to complete all cycles of docetaxel and 8 patients required dose reduction of docetaxel due to development of grade 3-4 mucositis and hand-foot syndrome. This observation prompted a protocol change requiring 3 weeks between doxorubicin and docetaxel. Primary chemotherapy with dose-dense doxorubicin and docetaxel given sequentially is well tolerated and allows a high rate of breast sparing in patients with large breast cancers.
authors.affiliation: Department of Medicine, University Hospitals of Cleveland, Cleveland, OH 44106, USA. bxc12@po.cwru.edu
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Cooper
authors.forename: Tomas
authors.initials: T
authors.lastname: Radivoyevitch
authors.forename: Beth A
authors.initials: BA
authors.lastname: Overmoyer
authors.forename: Robert R
authors.initials: RR
authors.lastname: Shenk
authors.forename: Huong T
authors.initials: HT
authors.lastname: Pham
authors.forename: Judith R
authors.initials: JR
authors.lastname: Samuels
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Parry
authors.forename: Paula
authors.initials: P
authors.lastname: Silverman
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / 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* / Q000473:pathology / Q000601:surgery; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011446:Prospective Studies; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin