title: Oxandrolone for the treatment of bone marrow failure in Fanconi anemia.
abstract: BACKGROUND
  A majority of Fanconi anemia (FA) patients will experience bone marrow failure (BMF) and androgen therapy (most often oxymetholone) may be utilized as a treatment to improve BMF-related cytopenias. However, oxymetholone is associated with toxicities making identification of other agents of interest. In this study we aimed to evaluate the toxicity profile and hematologic response in patients with FA who are treated with low-dose oxandrolone, a synthetic non-fluorinated anabolic steroid, similar to oxymetholone, with known dosing thresholds for virilization.
  
  
  METHODS
  A single arm, Phase I/II study was designed to treat patients on low-dose oxandrolone. If no toxicity or hematologic response was noted at 16 weeks, a single dose escalation was offered. Subjects were regularly assessed for toxicity, including determinations of virilization, behavioral changes, and liver and kidney function. At 32 weeks, those who demonstrated hematologic response were allowed to continue study treatment, and those without improvement were deemed non-responsive.
  
  
  RESULTS
  Nine subjects completed the study and were followed for a median of 99 weeks (46-136 weeks). Three (33.3%) subjects developed mild sub-clinical virilization and continued treatment with a dose reduction. None (0%) had adverse behavioral changes. Two (22.2%) developed elevated liver function tests at 42 and 105 weeks. Seven (77.8%) subjects had a hematologic response.
  
  
  CONCLUSIONS
  Oxandrolone appears to be well-tolerated, has limited toxicities at the administered doses in FA with patients, and may be an alternative androgen for the treatment of BMF in FA.
authors.affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Division of Endocrinology, Stanford University School of Medicine, Stanford, California.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rose
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Leslie
authors.initials: L
authors.lastname: Korbee
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Wilson
authors.forename: M Douglas
authors.initials: MD
authors.lastname: Ris
authors.forename: Ori
authors.initials: O
authors.lastname: Eyal
authors.forename: Rosa
authors.initials: R
authors.lastname: Sherafat-Kazemzadeh
authors.forename: Sureka
authors.initials: S
authors.lastname: Bollepalli
authors.forename: Richard
authors.initials: R
authors.lastname: Harris
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jeng
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.forename: Franklin O
authors.initials: FO
authors.lastname: Smith
mesh_terms: D045930:Anabolic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000741:Anemia, Aplastic; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D002648:Child; D005199:Fanconi Anemia / Q000150:complications*; D005260:Female; D006457:Hemoglobinuria, Paroxysmal / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D010074:Oxandrolone / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D045930:Anabolic Agents; D010074:Oxandrolone
keywords: Fanconi anemia; androgen; bone marrow failure; virilization