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

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The approach to the management of extracranial GCTs has been informed by the results of two intergroup studies conducted by the Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG).[6,7,11] These studies explored the use of PEB for the treatment of localized gonadal GCT [6] and the benefit of increasing the dose of cisplatin (high-dose [HD]-PEB: 200 mg/m2 vs. PEB: 100 mg/m2 of cisplatin) in a randomized manner in patients with extragonadal and advanced gonadal GCTs.[7]

The intensification of cisplatin in the HD-PEB regimen provided some improvement in EFS but no difference in OS; however, the use of HD-PEB was associated with a significantly higher incidence and severity of ototoxicity and nephrotoxicity. In a subsequent study, amifostine was not effective in preventing hearing loss in patients who received HD-PEB.[17]

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
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