title: Patterns of chemotherapy-induced toxicities in younger children and adolescents with rhabdomyosarcoma: a report from the Children's Oncology Group Soft Tissue Sarcoma Committee.
abstract: BACKGROUND
  Patients aged >10 years with rhabdomyosarcoma have an inferior outcome compared with patients ages 1 to 9 years, which may be explained by toxicities (adverse events [AEs]) that result in chemotherapy dose reductions.
  
  
  METHODS
  AEs observed during 1 of 3 randomized chemotherapy regimens (vincristine, dactinomycin, and cyclophosphamide [VAC]; vincristine, dactinomycin, and ifosfamide [VAI]; or vincristine, ifosfamide, and etoposide [VIE]) in the Fourth Intergroup Rhabdomyosarcoma Study were recorded. The incidence of toxicities by age and treatment regimen was determined. The odds of developing AEs in a particular age group (ages 5-9 years, 10-14 years, and 15-20 years) were compared with the odds in the control group of patients ages 1 to 4 years.
  
  
  RESULTS
  In total, 657 patients were eligible for analysis. The estimated 5-year event-free survival rates were 78%, 83%, 67%, and 58% for the groups ages 1 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 20 years, respectively. Patients ages 15 to 20 years experienced less neutropenia (odds ratio [OR], 0.43; P < .0001), thrombocytopenia (OR, 0.41; P < .0001), anemia (OR, 0.34; P < .0001), and infection (OR, 0.41; P < .0001) compared with younger patients, although they received similar amounts of chemotherapy. In contrast, peripheral nervous system toxicity was higher in adolescents aged >10 years (OR, 4.18; P < .0001). Females experienced more neutropenia (OR, 1.28; P = .05) and thrombocytopenia (OR, 1.26; P = .06) compared with males.
  
  
  CONCLUSIONS
  Adolescents who received treatment for rhabdomyosarcoma experienced significantly less hematologic toxicity and more peripheral nervous system toxicity compared with younger children despite receiving similar amounts of chemotherapy. Although outcomes were inferior in adolescents, it was unclear whether the differences in toxicity observed in the current study had an impact on outcome. The authors concluded that future studies examining the age-related and sex-related differences in pharmacokinetics of chemotherapy are necessary.
authors.affiliation: Department of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada. abha.gupta@sickkids.ca
authors.forename: Abha A
authors.initials: AA
authors.lastname: Gupta
authors.forename: James R
authors.initials: JR
authors.lastname: Anderson
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Pappo
authors.forename: Sheri L
authors.initials: SL
authors.lastname: Spunt
authors.forename: Roshni
authors.initials: R
authors.lastname: Dasgupta
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Indelicato
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Hawkins
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000740:Anemia / Q000139:chemically induced / Q000453:epidemiology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D015994:Incidence; D008297:Male; D015080:Mesna / Q000008:administration & dosage; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology*; D012208:Rhabdomyosarcoma / Q000188:drug therapy*; D012727:Sex Characteristics; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology*; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D003609:Dactinomycin; D015251:Epirubicin; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D015080:Mesna; D007069:Ifosfamide