title: Phase I trial of ixabepilone plus pegylated liposomal doxorubicin in patients with adenocarcinoma of breast or ovary.
abstract: BACKGROUND
  Ixabepilone is a semisynthetic epothilone B analogue that is active in taxane-resistant cell lines and has shown activity in patients with refractory breast and ovarian cancer. We carried out a phase I trial of ixabepilone plus pegylated liposomal doxorubicin (PLD) in patients with advanced taxane-pretreated ovarian and breast cancer.
  
  
  METHODS
  Patients with recurrent ovarian or breast carcinoma received PLD every 3 or 4 weeks plus five different dose schemas of ixabepilone in cohorts of three to six patients.
  
  
  RESULTS
  Thirty patients received a total of 142 treatment cycles of the PLD-ixabepilone combination. The recommended phase II dose and schedule of ixabepilone was 16 mg/m(2) on days 1, 8, and 15 plus PLD 30 mg/m(2) given on day 1, repeated every 4 weeks. Hand-foot syndrome and mucositis were dose limiting when both ixabepilone and PLD were given every 3 or 4 weeks. Objective responses were observed in 3 of 13 patients (23%) with breast cancer and 5 of 17 patients (29%) with ovarian cancer.
  
  
  CONCLUSIONS
  Ixabepilone may be safely combined with PLD, but tolerability is highly dependent upon the scheduling of both agents. This combination demonstrated efficacy in patients with breast and ovarian cancer and merits further evaluation in these settings.
authors.affiliation: Department of Medicine. Electronic address: elc2007@med.cornell.edu.
authors.forename: E
authors.initials: E
authors.lastname: Chuang
authors.affiliation: Department of Medicine.
authors.forename: N
authors.initials: N
authors.lastname: Wiener
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College, New York, NY.
authors.forename: P
authors.initials: P
authors.lastname: Christos
authors.affiliation: Department of Medicine.
authors.forename: R
authors.initials: R
authors.lastname: Kessler
authors.affiliation: Department of Medicine.
authors.forename: M
authors.initials: M
authors.lastname: Cobham
authors.affiliation: Department of Medicine.
authors.forename: D
authors.initials: D
authors.lastname: Donovan
authors.affiliation: Department of Obstetrics and Gynecology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: G L
authors.initials: GL
authors.lastname: Goldberg
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY.
authors.forename: T
authors.initials: T
authors.lastname: Caputo
authors.affiliation: Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD.
authors.forename: A
authors.initials: A
authors.lastname: Doyle
authors.affiliation: Department of Medicine.
authors.forename: L
authors.initials: L
authors.lastname: Vahdat
authors.affiliation: Department of Medicine and Gynecology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Sparano
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D034261:Epothilones / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D001952:Bridged-Ring Compounds; D034261:Epothilones; D043823:Taxoids; C506643:liposomal doxorubicin; C080625:taxane; D011092:Polyethylene Glycols; D004317:Doxorubicin; C430592:ixabepilone