title: Paclitaxel as second and subsequent therapy for metastatic breast cancer: activity independent of prior anthracycline response.
abstract: OBJECTIVE
  Two phase II clinical trials were performed to determine efficacy and tolerability of paclitaxel (Taxol; Bristol-Myers Squibb Co, Wallingford, CT) and granulocyte colony-stimulating factor ([G-CSF] Neupogen; Amgen, Inc, Thousand Oaks, CA) as second or subsequent therapy for metastatic breast cancer.
  
  
  METHODS
  Paclitaxel plus G-CSF was administered as a second stage IV regimen to 25 patients with metastatic breast cancer at a dose of 250 mg/m2 intravenously over 24 hours. Fifty-two patients received paclitoxel plus G-CSF at 200 mg/m2 as a third or subsequent regimen (no restriction on number of prior regimens or on prior high-dose chemotherapy). All patients had received prior anthracycline treatment, and ultimately had progressive bidimensionally measurable disease.
  
  
  RESULTS
  Twenty-five of 76 patients (32.8%) had a major objective response (95% confidence interval [CI], 14% to 37%). The median duration of response was 7 months (range, 1 to 20+). Responses were as likely in patients with disease demonstrated to be unresponsive to anthracycline, ie, de novo resistance (11 of 37, or 30%) as in those with disease that once exhibited anthracycline sensitivity, ie, acquired resistance, (10 of 31, or 32%). G-CSF administration was associated with febrile neutropenic episodes in 36 of 402 cycles (9%) in 16 of 76 patients (21%).
  
  
  CONCLUSIONS
  Paclitaxel's clinically significant activity against metastatic breast cancer extends to patients with many prior chemotherapy regimens. The lack of impact of prior doxorubicin therapy on the likelihood of subsequent response to paclitaxel suggests an important role for this agent in the treatment of refractory metastatic breast cancer.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Seidman
authors.forename: B S
authors.initials: BS
authors.lastname: Reichman
authors.forename: J P
authors.initials: JP
authors.lastname: Crown
authors.forename: T J
authors.initials: TJ
authors.lastname: Yao
authors.forename: V
authors.initials: V
authors.lastname: Currie
authors.forename: T B
authors.initials: TB
authors.lastname: Hakes
authors.forename: C A
authors.initials: CA
authors.lastname: Hudis
authors.forename: T A
authors.initials: TA
authors.lastname: Gilewski
authors.forename: J
authors.initials: J
authors.lastname: Baselga
authors.forename: P
authors.initials: P
authors.lastname: Forsythe
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004351:Drug Resistance; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel