Chemotherapy Protocols Without Radiation for Medulloblastomas in Infants

Head Start 2 Standard Risk (11)

Surgery

• Standard medulloblastoma surgery: Every attempt is made for an as near-total resection as possible, without attempting removal of tumor invading the brainstem. Serious consideration is given to reoperation when there is greater than 1 cm3 of tumor remaining after surgery.

Induction chemotherapy – five 21-day cycles

• Day 1: Cisplatin, 3.5 mg/kg IV
• Days 1, 8, 15: Vincristine, 0.05 mg/kg (cycles 1-3 only) IV
• Days 2 and 3: Cyclophosphamide, 65 mg/kg IV
• Days 2 and 3: Etopside, 4 mg/kg IV
• Cell harvest: Autologous peripheral stem cell harvest after cycle one

Re-evaluation

• Repeat imaging: The ultimate success of this protocol in managing medulloblastomas is dependent on whether or not there is residual tumor after induction chemotherapy. Consequently, the patient is re-imaged after completion of induction chemotherapy.
• Second-look surgery: Second-look surgery has been advocated to establish whether or not suspicious areas on imaging represent residual tumor after five cycles. Also in situations where only a partial resection was possible upfront, second-look surgery is considered after two or five cycles of induction to minimize the bulk of disease. It is not expected that the tumor is curable with chemotherapy alone if there is residual disease at the time of myeloablative therapy.

Submyeloablative/consolidation chemotherapy

• Days -5, -4, -3: Thiotepa, 300 mg/m2 IV
• Days -5, -4, -3: Etoposide, 250mg/m2 IV
• Days -8, -7, -6: Carboplatin, 500 mg/m2 IV (Calvert formula, area under the curve 7 mg/ml/min) per day
• Day 0 (72 hours after chemotherapy completed): Autologous peripheral blood stem cell infusion
• G-CSF: All patients receive G-CSF, 5 µg/kg/day, starting 24 hours after stem cell infusion.

Head Start 2 High Risk (7)

Induction chemotherapy – Five 21-day cycles

• Day 1: Cisplatin, 3.5 mg/kg IV
• Days 1, 8, and 15: Vincristine, 0.05 mg/kg IV, for the first three cycles only for a total of nine doses
• Days 2 and 3: Etoposide, 4 mg/kg/day IV, followed by cyclophosphamide, 65 mg/kg/day, with mesna 20% of cyclophosphamide dose at hours 0. 3 and 6.
• Day 4: Methotrexate, 400 mg/kg IV, with leukovorin rescue given until serum methotrexate is less than 0.1 M. G-CSF is then administered subcutaneously 24 hours later and is continued until there has been recovery of the neutrophil count.

Re-evaluation

• Repeat imaging: The ultimate success of this protocol in managing medulloblastomas is dependent on whether or not there is residual tumor after induction chemotherapy. Consequently, the patient is re-imaged after completion of the induction chemotherapy cycle.
• Consolidation if no disease: If there is no evidence of residual tumor, the patient proceeds directly to consolidation myeloablative chemotherapy.
• Palliation or alternate treatment if disease: If there is residual disease, an alternative approach should be considered such as palliation, or expectation to treat with a radiation therapy regimen if there is an intent to potentially cure, and this is considered acceptable in terms of the long-term morbidity that would be expected with the child’s age.

Submyeloablative/consolidation chemotherapy

• See Headstart Protocol: As per Head Start Standard-Risk Medulloblastoma Submyeloablative /Consolidation.
• Autologous stem cell infusion

German Protocol

German Pediatric Brain Tumor Study Group Trial (HIT-SKK’92) (27)

Three cycles of the following

• Week 1: Methotrexate, 2 mg/day intraventricular, on days 1–4, Cyclophosphamide, 800 mg/m2/day IV, on days 1–3, Vincristine, 1.5 mg/m2 IV on day 1
• Week 3: Methotrexate,2 mg/day intraventricular on days 1–4, Methotrexate, 5 g/m2/day IV, 24 hours, Vincristine, 1.5 mg/m2 IV, on day 1
• Week 5: Methotrexate, 2 mg/day intraventricular, on days 1–4,  Methotrexate, 5 g/ m2/day IV, 24 hours, Vincristine, 1.5 mg/m2 IV, on day 1
• Week 7: Methotrexate,2 mg/day intraventricular on days 1–4,  Carboplatin, 200 mg/ m2/day IV, on days 1-3, Etoposide. 150 mg/m2 IV, on days 1-3