title: First-day step-down to oral outpatient treatment versus continued standard treatment in children with cancer and low-risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study.
abstract: BACKGROUND
  The standard treatment of fever in chemotherapy-induced neutropenia (FN) includes emergency hospitalization and empirical intravenous antimicrobial therapy. This study determined if first-day step-down to oral outpatient treatment is not inferior to continued standard regarding safety and efficacy in children with low-risk FN.
  
  
  METHODS
  In a randomized controlled non-blinded multicenter study, pediatric patients with FN after non-myeloablative chemotherapy were reassessed after 8-22 hours of inpatient intravenous antimicrobial therapy. Low-risk patients were randomized to first-day step-down to experimental (outpatient, oral amoxicillin plus ciprofloxacin) versus continued standard treatment. Exact non-inferiority tests were used for safety (no serious medical complication; non-inferiority margin of difference, 3.5%) and efficacy (resolution of infection without recurrence, no modification of antimicrobial therapy, no adverse event; 10%).
  
  
  RESULTS
  In 93 (26%) of 355 potentially eligible FN episodes low-risk criteria were fulfilled, and 62 were randomized, 28 to experimental (1 lost to follow-up) and 34 to standard treatment. In intention-to-treat analyses, non-inferiority was not proven for safety [27 of 27 (100%) vs. 33 of 34 (97%; 1 death) episodes; 95% upper confidence border, 6.7%; P = 0.11], but non-inferiority was proven for efficacy [23 of 27 (85%) vs. 26 of 34 (76%) episodes; 95% upper confidence border, 9.4%; P = 0.045]. Per-protocol analyses confirmed these results.
  
  
  CONCLUSIONS
  In children with low-risk FN, the efficacy of first-day step-down to oral antimicrobial therapy with amoxicillin and ciprofloxacin in an outpatient setting was non-inferior to continued hospitalization and intravenous antimicrobial therapy. The safety of this procedure, however, was not assessable with sufficient power.
authors.affiliation: Department of Pediatrics, University of Bern, Bern, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Brack
authors.forename: Nicole
authors.initials: N
authors.lastname: Bodmer
authors.forename: Arne
authors.initials: A
authors.lastname: Simon
authors.forename: Kurt
authors.initials: K
authors.lastname: Leibundgut
authors.forename: Thomas
authors.initials: T
authors.lastname: Kühne
authors.forename: Felix K
authors.initials: FK
authors.lastname: Niggli
authors.forename: Roland A
authors.initials: RA
authors.lastname: Ammann
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000553:Ambulatory Care / Q000379:methods*; D000658:Amoxicillin / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000592:standards*; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications*; D012306:Risk
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002939:Ciprofloxacin; D000658:Amoxicillin