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Childhood Extracranial Germ Cell Tumors Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment Background for Childhood Extracranial GCTs

Table 4. Comparison of Pediatric PEB and JEB Chemotherapy Dosing Schedulesa

RegimenBleomycinEtoposideCisplatinCarboplatinReferences
GFR = glomerular filtration rate; JEB = carboplatin, etoposide, and bleomycin; PEB = cisplatin, etoposide, and bleomycin.
a Adult doses of PEB and JEB chemotherapy are different from pediatric doses.
Pediatric PEB (every 21 days)15 units/m², day 1100 mg/m², days 1–520 mg/m², days 1–5 [6,7]
Pediatric JEB (every 21–28 days)15 units/m², day 3120 mg/m², days 1–3 600 mg/m² or GFR-based dosing, day 2[8]

Table 5 provides an overview of standard treatment options for children with extracranial GCTs. Treatment requires a multidisciplinary approach with various surgical subspecialties and pediatric oncologists. Specific details of treatment by primary site and clinical condition are described in subsequent sections.

Table 5. Standard Treatment Approaches for Infants and Children Younger Than 15 Years With Germ Cell Tumors by Histology, Stage, and Primary Site

HistologyPrimary SiteStageTreatment
PEB = cisplatin, etoposide, and bleomycin.
a Patients aged 15 years and older with stage IV testicular tumors and all patients with stages III and IV extragonadal tumors treated with PEB have suboptimal outcome and should be considered for more intensive therapies.
b The role for observation after surgery has not been well established for stage I ovarian germ cell tumors and should be reserved for a clinical trial.
c The role for surgery at diagnosis for extragonadal tumors is age- and site-dependent and must be individualized. Depending on the clinical setting, the appropriate surgical approach may range from no surgery (e.g., mediastinal primary tumor in a patient with a compromised airway and elevated tumor markers), to biopsy, to primary resection. In some cases, an appropriate strategy is biopsy at diagnosis followed by subsequent surgery in selected patients who have residual masses following chemotherapy.
Mature teratomaAll sitesLocalizedSurgery + Observation
Immature teratomaAll sitesLocalizedSurgery + Observation
Malignant germ cell tumorsTesticularStage ISurgery + Observation
Stages II–IVaSurgery + PEB
 OvarianStage IbSurgery + PEB
Stages II–IVSurgery + PEB
ExtragonadalStages I–IISurgeryc + PEB
Stages III–IVaSurgeryc + PEB

Non-GCT Malignant Elements

The treatment of GCTs with other non-GCT elements is complex and scant data exist to inform treatment. Specific treatment for both the malignant GCT and non-GCT elements may be required.[18] However, the optimal treatment strategy for other malignant elements found in GCT has not been determined.

References:

  1. Kurman RJ, Norris HJ: Endodermal sinus tumor of the ovary: a clinical and pathologic analysis of 71 cases. Cancer 38 (6): 2404-19, 1976.
  2. Chretien PB, Milam JD, Foote FW, et al.: Embryonal adenocarcinomas (a type of malignant teratoma) of the sacrococcygeal region. Clinical and pathologic aspects of 21 cases. Cancer 26 (3): 522-35, 1970.
  3. Billmire DF, Grosfeld JL: Teratomas in childhood: analysis of 142 cases. J Pediatr Surg 21 (6): 548-51, 1986.
  4. Hawkins EP, Finegold MJ, Hawkins HK, et al.: Nongerminomatous malignant germ cell tumors in children. A review of 89 cases from the Pediatric Oncology Group, 1971-1984. Cancer 58 (12): 2579-84, 1986.
  5. Marina N, Fontanesi J, Kun L, et al.: Treatment of childhood germ cell tumors. Review of the St. Jude experience from 1979 to 1988. Cancer 70 (10): 2568-75, 1992.
  6. Rogers PC, Olson TA, Cullen JW, et al.: Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup Study--Pediatric Oncology Group 9048 and Children's Cancer Group 8891. J Clin Oncol 22 (17): 3563-9, 2004.
  7. Cushing B, Giller R, Cullen JW, et al.: Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study--Pediatric Oncology Group 9049 and Children's Cancer Group 8882. J Clin Oncol 22 (13): 2691-700, 2004.
  8. Mann JR, Raafat F, Robinson K, et al.: 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. J Clin Oncol 18 (22): 3809-18, 2000.
  9. Göbel U, Schneider DT, Calaminus G, et al.: Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89. J Clin Oncol 19 (7): 1943-50, 2001.
  10. Rescorla FJ: Pediatric germ cell tumors. Semin Surg Oncol 16 (2): 144-58, 1999.
  11. Marina NM, Cushing B, Giller R, et al.: Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study. J Clin Oncol 17 (7): 2137-43, 1999.
  12. Schlatter M, Rescorla F, Giller R, et al.: Excellent outcome in patients with stage I germ cell tumors of the testes: a study of the Children's Cancer Group/Pediatric Oncology Group. J Pediatr Surg 38 (3): 319-24; discussion 319-24, 2003.
  13. de Wit R, Roberts JT, Wilkinson PM, et al.: Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol 19 (6): 1629-40, 2001.
  14. Gershenson DM, Morris M, Cangir A, et al.: Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin. J Clin Oncol 8 (4): 715-20, 1990.
  15. Stern JW, Bunin N: Prospective study of carboplatin-based chemotherapy for pediatric germ cell tumors. Med Pediatr Oncol 39 (3): 163-7, 2002.
  16. Horwich A, Sleijfer DT, Fosså SD, et al.: Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial. J Clin Oncol 15 (5): 1844-52, 1997.
  17. Marina N, Chang KW, Malogolowkin M, et al.: Amifostine does not protect against the ototoxicity of high-dose cisplatin combined with etoposide and bleomycin in pediatric germ-cell tumors: a Children's Oncology Group study. Cancer 104 (4): 841-7, 2005.
  18. Ehrlich Y, Beck SD, Ulbright TM, et al.: Outcome analysis of patients with transformed teratoma to primitive neuroectodermal tumor. Ann Oncol 21 (9): 1846-50, 2010.
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Last Updated: February 25, 2014
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