title: A detailed evaluation of cardiac toxicity: a phase II study of doxorubicin and one- or three-hour-infusion paclitaxel in patients with metastatic breast cancer.
abstract: OBJECTIVE
  This Phase II study was designed to determine the efficacy and toxicity of combination doxorubicin and paclitaxel as front-line treatment for metastatic breast cancer.
  
  
  METHODS
  Eligible patients had no prior anthracycline or taxane therapy and normal cardiac function. They were treated with bolus doxorubicin 60 mg/m2, followed by paclitaxel 200 mg/m2, as either 1- or 3-h infusions for six to seven cycles. Single-agent paclitaxel was continued thereafter. Serial multiple gated acquisition scans were performed, and endomyocardial biopsies were performed for consenting patients.
  
  
  RESULTS
  Eighty-two patients were enrolled with a median age of 53 years (range, 32-78 years). Of 79 evaluable patients, 58.2% had an objective response (3.8% complete response + 54.4% partial response), 34.2% had stable disease, and 7.6% had progressive disease. With median follow-up of 37.5 months, median time to progression was 7 months; median survival was 31 months. Multiple gated acquisition scans were performed in 82 of 82 patients at baseline, 75 of 82 patients at a total doxorubicin dose of 60-180 mg/m2, 62 of 68 patients at 200-300 mg/m2, 18 of 52 patients at 310-360 mg/m2, and 4 of 8 patients at 420 mg/m2. Median ejection fractions were 62.5, 60, 57.5, 52.5, and 32%, respectively. Fifteen of 82 (18.3%) patients had a decrease in ejection fraction > or = 15% to an absolute ejection fraction < or = 50%. Eight of these 15 patients (53%) developed clinical congestive heart failure: 4 of 8 (50%) who received a total doxorubicin dose of 420 mg/m2 versus 4 of 74 (5.4%) who received a dose < or = 360 mg/m2 (P = 0.002).
  
  
  CONCLUSIONS
  When the doxorubicin dose exceeds 360 mg/m2, the combination of bolus doxorubicin and paclitaxel presents unacceptable cardiac risk.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Sharon H
authors.initials: SH
authors.lastname: Giordano
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Booser
authors.forename: James L
authors.initials: JL
authors.lastname: Murray
authors.forename: Nuhad K
authors.initials: NK
authors.lastname: Ibrahim
authors.forename: Zia U
authors.initials: ZU
authors.lastname: Rahman
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Richard L
authors.initials: RL
authors.lastname: Theriault
authors.forename: Marguerite F
authors.initials: MF
authors.lastname: Rosales
authors.forename: Edgardo
authors.initials: E
authors.lastname: Rivera
authors.forename: Debbie
authors.initials: D
authors.lastname: Frye
authors.forename: Michael
authors.initials: M
authors.lastname: Ewer
authors.forename: Nelson G
authors.initials: NG
authors.lastname: Ordonez
authors.forename: Aman U
authors.initials: AU
authors.lastname: Buzdar
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D017239:Paclitaxel