title: A phase I/II study of neoadjuvant liposomal doxorubicin, paclitaxel, and hyperthermia in locally advanced breast cancer.
abstract: OBJECTIVE
  The prognosis for locally advanced breast cancer (LABC) patients continues to be poor, with an estimated five-year survival of only 50-60%. Preclinical data demonstrates enhanced therapeutic efficacy with liposomal encapsulation of doxorubicin combined with hyperthermia (HT). Therefore this phase I/II study was designed to evaluate the safety and efficacy of a novel neoadjuvant combination treatment of paclitaxel, liposomal doxorubicin, and hyperthermia.
  
  
  METHODS
  Eligible patients received four cycles of neoadjuvant liposomal doxorubicin (30-75 mg/m(2)), paclitaxel (100-175 mg/m(2)), and hyperthermia. They subsequently underwent either a modified radical mastectomy or lumpectomy with axillary node dissection followed by radiation therapy and then eight cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy.
  
  
  RESULTS
  Forty-seven patients with stage IIB-III LABC were enrolled and 43 patients were evaluable. Fourteen patients (33%) had inflammatory breast cancer. Combined (partial + complete) clinical response rate was 72% and combined pathological response rate was 60%. Four patients achieved a pathologically complete response. Sixteen patients were eligible for breast-conserving surgery. The cumulative equivalent minutes (CEM 43) at T90 (tenth percentile of temperature distribution) was significantly greater for those with a pathological response. Four-year disease-free survival was 63% (95% CI, 46%-76%) and the four-year overall survival was 75% (95% CI, 58-86%).
  
  
  CONCLUSIONS
  Neoadjuvant therapy using paclitaxel, liposomal doxorubicin and hyperthermia is a feasible and well tolerated treatment strategy in patients with LABC. The thermal dose parameter CEM 43 T90 was significantly correlated with attaining a pathological response.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA. vujas@radonc.duke.edu
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
authors.forename: Dong W
authors.initials: DW
authors.lastname: Kim
authors.forename: Ellen
authors.initials: E
authors.lastname: Jones
authors.forename: Lan
authors.initials: L
authors.lastname: Lan
authors.forename: Linda
authors.initials: L
authors.lastname: McCall
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: Oana
authors.initials: O
authors.lastname: Craciunescu
authors.forename: Paul
authors.initials: P
authors.lastname: Stauffer
authors.forename: Vlayka
authors.initials: V
authors.lastname: Liotcheva
authors.forename: Allison
authors.initials: A
authors.lastname: Betof
authors.forename: Kimberly
authors.initials: K
authors.lastname: Blackwell
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D017239:Paclitaxel