title: Revisiting the role of doxorubicin in the treatment of rhabdomyosarcoma: an up-front window study in newly diagnosed children with high-risk metastatic disease.
abstract: OBJECTIVE
  Many cooperative groups have reported on the chemo-sensitivity of rhabdomyosarcoma (RMS). Doxorubicin has been tested but remains a controversial treatment option. We report here the results of the up-front evaluation of the efficacy of doxorubicin in children and adolescents with high-risk metastatic RMS.
  
  
  METHODS
  Patients younger than 18 years of age (>6 months) with newly diagnosed, histologically confirmed high-risk metastatic RMS were required to have measurable disease, to have undergone no prior chemotherapy or radiation therapy and to have normal liver, renal and cardiac function before treatment. Doxorubicin was administered intravenously over 48h to a total dose of 60mg/m2. Two courses were given separated by a 21day interval. Response to therapy was assessed by diagnostic imaging after the second course. The study was designed as a two-stage procedure according to the multistep plan described by Fleming.
  
  
  RESULTS
  Twenty patients were eligible for analysis. Median age at diagnosis was 9.8 years (range from 2 to 16). Thirteen of the 20 patients treated in the first step responded to treatment, corresponding to an overall response to doxorubicin of 65% [95% confidence interval (CI), 44-85%]. The rates of CR and PR were 5% [95% CI, 0-14%] and 60% [95% CI, 39-81%], respectively. Four (20%) patients had progressive disease, corresponding to a progression rate of 20% [95% CI, 2-38%].
  
  
  CONCLUSIONS
  This window study provides the definitive demonstration of the efficacy of doxorubicin in untreated RMS. Given the inconclusive results obtained from previous studies using differing schedules chemotherapy incorporating doxorubicin, the next step should be a randomised study testing dose intensity in high-risk localised RMS. This issue is being addressed in a current European study (EpSSG RMS 2005).
authors.affiliation: Centre Léon Bérard, Paediatric Oncology Unit, 28 Rue Laennec, 69373 Lyon Cedex 08, France. bergeron@lyon.fnclcc.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Bergeron
authors.forename: Philippe
authors.initials: P
authors.lastname: Thiesse
authors.forename: Annie
authors.initials: A
authors.lastname: Rey
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.forename: Patrick
authors.initials: P
authors.lastname: Boutard
authors.forename: Caroline
authors.initials: C
authors.lastname: Thomas
authors.forename: Claudine
authors.initials: C
authors.lastname: Schmitt
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Scopinaro
authors.forename: Frederic
authors.initials: F
authors.lastname: Bernard
authors.forename: Michael
authors.initials: M
authors.lastname: Stevens
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin