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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

From the Birmingham Children’s Hospital, Birmingham; United Kingdom Children’s Cancer Study Group Data Centre and University of Leicester, Leicester; City Hospital, Nottingham; Medical School, Aberdeen; Institute of Child Health, Newcastle-upon-Tyne; and Royal Hospital for Sick Children, Bristol, United Kingdom.

Address reprint requests to J.R. Mann, FRCP, Oncology Department, Birmingham Children’s Hospital, Steelhouse Lane, Birmingham B4 6NH, United Kingdom; email jill.mann{at}bhamchildrens.wmids nhs.uk.

PURPOSE: To evaluate carboplatin, etoposide, and bleomycin (JEB) in children with malignant extracranial germ cell tumors (GCTs).

PATIENTS AND 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/m² on days 1 through 3, carboplatin 600 mg/m² on day 2, and bleomycin 15 mg/m² 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.

CONCLUSION: Conservative surgery, a watch-and-wait approach after complete excision, and JEB for those requiring chemotherapy produced high cure rates and few serious complications.

The Cancer Research Campaign, London, United Kingdom, provided financial support for data management.

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