title: Efficacy of ifosfamide and doxorubicin given as a phase II "window" in children with newly diagnosed metastatic rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study Group.
abstract: BACKGROUND
  The cure rate for children/adolescents with localized rhabdomyosarcoma (RMS) has tripled over the past 25 years, but patients with metastatic disease at presentation have not benefited similarly, and urgently need new therapy. We evaluated a new drug pair, ifosfamide + doxorubicin, for such patients.
  
  
  METHODS
  We estimated the complete and partial response rates (i.e., CR and PR) of 152 previously untreated children/adolescents with metastatic RMS entered on the IRS-IV pilot from July 1988 to October 1991 who received an "up-front window" of ifosfamide (1.8 gm/m(2)/day for 5 days) and doxorubicin (30 mg/m(2)/day for 2 days) given every 3 weeks for 12 weeks. This was followed by combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide (VAC), given every 3 weeks for an additional 36 weeks.
  
  
  RESULTS
  Of 115 patients evaluable for early response at 12 weeks, 28 (20%) had CR and 66 (43%) had PR. The ultimate CR rate was 52%. Overall, about one-third of patients survived. Prognostic factor analysis revealed that patients < 10 years old (P < 0.001), those with embryonal tumors (P = 0.002), or a GU primary site (P = 0.010), and those who lacked nodal disease (P = 0.041), and those who lacked bone or bone marrow metastasis (P < 0.001) fared better than did others.
  
  
  CONCLUSIONS
  The 63% CR + PR rate achieved at 12 weeks and overall 5-year FFS seen with this drug pair is similar to that achieved with previously evaluated drug combinations. We conclude that ifosfamide/doxorubicin is highly active in advanced RMS, and should be considered for inclusion in frontline therapy for children with intermediate or high-risk RMS.
authors.affiliation: Intergroup Rhabdomyosarcoma Study Group Operations Office, Children's Oncology Group, Arcadia, CA 91066-6012, USA. smason@nccf.org
authors.forename: E
authors.initials: E
authors.lastname: Sandler
authors.forename: E
authors.initials: E
authors.lastname: Lyden
authors.forename: F
authors.initials: F
authors.lastname: Ruymann
authors.forename: H
authors.initials: H
authors.lastname: Maurer
authors.forename: M
authors.initials: M
authors.lastname: Wharam
authors.forename: D
authors.initials: D
authors.lastname: Parham
authors.forename: M
authors.initials: M
authors.lastname: Link
authors.forename: W
authors.initials: W
authors.lastname: Crist
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009362:Neoplasm Metastasis; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000473:pathology; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D007069:Ifosfamide