ICE Chemotherapy in Intracranial Germinoma
ICE chemotherapy (ifosfamide, carboplatin, etoposide) is given as first-line treatment for intracranial germinoma in combination with reduced-field radiotherapy, specifically to avoid craniospinal irradiation while maintaining excellent cure rates. 1, 2, 3
Primary Treatment Strategy
ICE is used upfront for localized intracranial germinoma to enable focal radiotherapy (40 Gy to the primary tumor site) instead of full craniospinal irradiation, thereby reducing long-term neurocognitive and endocrine toxicity while preserving 96-98% event-free survival rates. 1, 2, 3
Standard ICE Regimen for Germinoma
The typical protocol consists of:
- Alternating cycles: Carboplatin (600 mg/m²) + etoposide (150 mg/m² days 1-3) alternating with ifosfamide (1.8 g/m² days 22-26) + etoposide (150 mg/m² days 22-24) 2
- Total duration: 2-4 cycles of chemotherapy followed by focal radiotherapy 1, 2, 3
- Radiation field: 40 Gy to the initial tumor volume only, avoiding craniospinal fields 2, 3
Clinical Context and Evidence
The SIOP CNS GCT 96 trial demonstrated that chemotherapy (carboplatin/etoposide alternating with etoposide/ifosfamide) followed by local radiotherapy achieved 88% progression-free survival at 5 years in localized germinoma, compared to 97% with reduced-dose craniospinal irradiation alone. 1 However, the overall survival and event-free survival were equivalent between approaches. 1
French Society of Pediatric Oncology studies showed 98% 3-year survival and 96.4% event-free survival using this combined modality approach, with results equivalent to extensive radiotherapy but avoiding craniospinal fields. 2, 3
Critical Pattern of Failure
A major caveat: 6 of 7 relapses in the chemotherapy + focal RT group occurred in the ventricles outside the primary radiotherapy field, suggesting the radiation field should include the ventricular system even when using chemotherapy. 1 This represents a critical pitfall—focal RT to tumor bed alone may be insufficient.
When ICE is NOT Used
ICE is not standard salvage therapy for relapsed germinoma. The evidence provided focuses on ICE in other malignancies (lymphoma, gestational trophoblastic disease, testicular germ cell tumors) for salvage settings 4, but these contexts do not apply to intracranial germinoma's unique biology and treatment paradigm.
For metastatic germinoma at diagnosis, reduced-dose craniospinal irradiation (with optional preceding chemotherapy) remains the standard, achieving 98% event-free survival. 1
Toxicity Considerations
Dominant toxicity is hematological, with all patients experiencing grade 3-4 myelosuppression and granulocytopenic fever requiring hospitalization in 67% of courses. 5 Patients with diabetes insipidus (common in suprasellar germinomas) frequently develop electrolyte disturbances during chemotherapy requiring close monitoring. 3