title: Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies.
abstract: OBJECTIVE
  Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days.
  
  
  METHODS
  Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m(2) per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths.
  
  
  RESULTS
  Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred.
  
  
  CONCLUSIONS
  Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; denise.adams@cchmc.org.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Adams
authors.affiliation: University of Cincinnati, Cincinnati, Ohio;
authors.forename: Cameron C
authors.initials: CC
authors.lastname: Trenor
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts;
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Hammill
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts;
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vinks
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts;
authors.forename: Manish N
authors.initials: MN
authors.lastname: Patel
authors.affiliation: University of Cincinnati, Cincinnati, Ohio;
authors.forename: Gulraiz
authors.initials: G
authors.lastname: Chaudry
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors.forename: Mary Sue
authors.initials: MS
authors.lastname: Wentzel
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors.forename: Paula S
authors.initials: PS
authors.lastname: Mobberley-Schuman
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Campbell
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors.forename: Christine
authors.initials: C
authors.lastname: Brookbank
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts;
authors.forename: Anita
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors.forename: Carol
authors.initials: C
authors.lastname: Chute
authors.affiliation: University of Cincinnati, Cincinnati, Ohio;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Eile
authors.affiliation: University of Cincinnati, Cincinnati, Ohio;
authors.forename: Jesse
authors.initials: J
authors.lastname: McKenna
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts;
authors.forename: Arnold C
authors.initials: AC
authors.lastname: Merrow
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors.forename: Lin
authors.initials: L
authors.lastname: Fei
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors.forename: Lindsey
authors.initials: L
authors.lastname: Hornung
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors.forename: Michael
authors.initials: M
authors.lastname: Seid
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts;
authors.forename: A Roshni
authors.initials: AR
authors.lastname: Dasgupta
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts;
authors.forename: Belinda H
authors.initials: BH
authors.lastname: Dickie
authors.affiliation: Dayton Children's Medical Center, Dayton, Ohio; and.
authors.forename: Ravindhra G
authors.initials: RG
authors.lastname: Elluru
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors.forename: Anne W
authors.initials: AW
authors.lastname: Lucky
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts;
authors.forename: Brian
authors.initials: B
authors.lastname: Weiss
authors.affiliation: Omaha Children's Hospital and Medical Center, Omaha, Nebraska.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Azizkhan
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D011788:Quality of Life; D020123:Sirolimus / Q000097:blood / Q000627:therapeutic use*; D054079:Vascular Malformations / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus