title: A Phase I clinical trial of ixabepilone (BMS-247550), an epothilone B analog, administered intravenously on a daily schedule for 3 days.
abstract: BACKGROUND
  The epothilones are a novel class of microtubule-stabilizing agents. Ixabepilone (BMS-247550; NSC 710428) is a semisynthetic analog of the natural product epothilone B. The authors conducted a Phase I study by administering ixabepilone to patients as a 1-hour intravenous infusion daily for 3 consecutive days every 21 days.
  
  
  METHODS
  Twenty-six patients were enrolled and received ixabepilone at a starting dose of 8 or 10 mg/m(2) per day for 3 consecutive days.
  
  
  RESULTS
  One hundred and nineteen cycles were administered to 26 patients. The maximum-tolerated dose was 8 mg/m(2) per day of ixabepilone administered as a 1-hour intravenous infusion daily for 3 consecutive days every 21 days. The dose-limiting toxicity (DLT) was neutropenia. Other nonhematologic Grade 3 toxicities included fatigue (3 cycles), hyponatremia (1 cycle), anorexia (1 cycle), ileus (1 cycle), stomatitis (1 cycle), and emesis (1 cycle). Prolonged disease stabilization was observed in patients with mesothelioma, ovarian carcinoma, and renal cell carcinoma.
  
  
  CONCLUSIONS
  The recommended Phase II dose of ixabepilone on the daily schedule for 3 days was 8-10 mg/m(2) per day. Neutropenia was the DLT. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting.
authors.affiliation: Cancer Therapeutics Branch, Center of Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Sen H
authors.initials: SH
authors.lastname: Zhuang
authors.forename: Manish
authors.initials: M
authors.lastname: Agrawal
authors.forename: Maureen
authors.initials: M
authors.lastname: Edgerly
authors.forename: Susan
authors.initials: S
authors.lastname: Bakke
authors.forename: Herb
authors.initials: H
authors.lastname: Kotz
authors.forename: Paul
authors.initials: P
authors.lastname: Thambi
authors.forename: Ann
authors.initials: A
authors.lastname: Rutt
authors.forename: Frank M
authors.initials: FM
authors.lastname: Balis
authors.forename: Susan
authors.initials: S
authors.lastname: Bates
authors.forename: Tito
authors.initials: T
authors.lastname: Fojo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004334:Drug Administration Schedule; D034261:Epothilones / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D034261:Epothilones; C430592:ixabepilone