title: Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.
abstract: OBJECTIVE
  This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma.
  
  
  METHODS
  One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival.
  
  
  RESULTS
  Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012).
  
  
  CONCLUSIONS
  Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.
authors.affiliation: Intergroup Rhabdomyosarcoma Study Group, Children's Cancer Group, Arcadia, California, USA. breit003@mc.duke.edu
authors.forename: P P
authors.initials: PP
authors.lastname: Breitfeld
authors.forename: E
authors.initials: E
authors.lastname: Lyden
authors.forename: R B
authors.initials: RB
authors.lastname: Raney
authors.forename: L A
authors.initials: LA
authors.lastname: Teot
authors.forename: M
authors.initials: M
authors.lastname: Wharam
authors.forename: T
authors.initials: T
authors.lastname: Lobe
authors.forename: W M
authors.initials: WM
authors.lastname: Crist
authors.forename: H M
authors.initials: HM
authors.lastname: Maurer
authors.forename: S S
authors.initials: SS
authors.lastname: Donaldson
authors.forename: F B
authors.initials: FB
authors.lastname: Ruymann
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D001989:Bronchiolitis Obliterans / Q000139:chemically induced; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D007674:Kidney Diseases / Q000139:chemically induced; D015993:Life Tables; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D009362:Neoplasm Metastasis; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D018805:Sepsis / Q000209:etiology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D008558:Melphalan; D007069:Ifosfamide