title: The United Kingdom Children's Cancer Study Group's second germ cell tumor study: carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity.
abstract: OBJECTIVE
  To evaluate carboplatin, etoposide, and bleomycin (JEB) in children with malignant extracranial germ cell tumors (GCTs).
  
  
  METHODS
  Malignant GCTs in children aged 0 to 16 years were excised without major morbidity or otherwise biopsied. Stage I testicular and some ovarian GCTs were resected and monitored with alpha-fetoprotein (AFP) ("watch-and-wait" approach). Patients with recurrent stage I disease and all other patients received JEB (etoposide 120 mg/m(2) on days 1 through 3, carboplatin 600 mg/m(2) on day 2, and bleomycin 15 mg/m(2) on day 3). Courses were administered every 3 to 4 weeks until remission, and then two more courses were given. Chemotherapy toxicities were assessed using World Health Organization or Brock grading.
  
  
  RESULTS
  Between January 1989 and December 1997, 192 patients were registered. Eight were excluded because either there was no histologic diagnosis (n = 3) or chemotherapy was given off-study (n = 5). The remaining 184 patients had germinoma (n = 20), malignant teratoma (n = 55), embryonal carcinoma (n = 1), yolk sac tumor (n = 107), or choriocarcinoma (n = 1). Forty-seven patients were treated with surgery alone, and 137 patients received JEB. The 5-year survival rate in March 1999 for all 184 patients was 93.2% (95% confidence interval [CI], 87.9% to 96.3%); for the 137 JEB-treated patients, it was 90.9% (95% CI, 83.9% to 95.0%), with an event-free survival rate of 87.8% (95% CI, 81.1% to 92.4%). The median follow-up after JEB treatment was 53 months (range, 0 to 109 months); the median number of courses was five (range, three to eight). Site, stage, and AFP level had prognostic significance. Nonfatal hematologic toxicity was common, but deafness and pulmonary and renal toxicities were rare. One child died of a thoracic tumor and bronchopulmonary dysplasia, and another died of acute myeloid leukemia.
  
  
  CONCLUSIONS
  Conservative surgery, a watch-and-wait approach after complete excision, and JEB for those requiring chemotherapy produced high cure rates and few serious complications.
authors.affiliation: Oncology Department, Birmingham Children's Hospital, Birmingham, United Kingdom. jill.mann@bhamchildrens.wmids.nhs.uk
authors.forename: J R
authors.initials: JR
authors.lastname: Mann
authors.forename: F
authors.initials: F
authors.lastname: Raafat
authors.forename: K
authors.initials: K
authors.lastname: Robinson
authors.forename: J
authors.initials: J
authors.lastname: Imeson
authors.forename: P
authors.initials: P
authors.lastname: Gornall
authors.forename: M
authors.initials: M
authors.lastname: Sokal
authors.forename: E
authors.initials: E
authors.lastname: Gray
authors.forename: P
authors.initials: P
authors.lastname: McKeever
authors.forename: J
authors.initials: J
authors.lastname: Hale
authors.forename: S
authors.initials: S
authors.lastname: Bailey
authors.forename: A
authors.initials: A
authors.lastname: Oakhill
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D006063:Chorionic Gonadotropin / Q000097:blood; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018237:Germinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016019:Survival Analysis; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; D001761:Bleomycin; D005047:Etoposide; D016190:Carboplatin