What are the dosing recommendations for cisplatin, cyclophosphamide (CY), and vincristine in the St. Jude protocol for medulloblastoma?

St. Jude Protocol Dosing for Average-Risk Medulloblastoma

The St. Jude protocol for average-risk medulloblastoma uses vincristine 1.4 mg/m² IV weekly during craniospinal irradiation, followed by maintenance chemotherapy with vincristine 1.4 mg/m² IV on days 1,8, and 15, cisplatin 70 mg/m² IV on day 1, and cyclophosphamide 1000 mg/m² IV on days 1 and 2, repeated every 28 days for 8 cycles. 1

Radiation Phase Dosing

• Vincristine: 1.4 mg/m² IV (maximum 2 mg) administered weekly during the 6-week craniospinal irradiation period 1
• Radiation dose: 23.4 Gy to the craniospinal axis, followed by an involved field boost to 54 Gy total to the primary tumor site 1

Maintenance Chemotherapy Phase

The maintenance regimen consists of three drugs administered in 28-day cycles for a total of 8 cycles:

• Vincristine: 1.4 mg/m² IV (maximum 2 mg) on days 1,8, and 15 of each cycle 1
• Cisplatin: 70 mg/m² IV on day 1 of each cycle 2
• Cyclophosphamide: 1000 mg/m² IV on days 1 and 2 of each cycle 2

Critical Protocol Distinctions

The St. Jude protocol differs fundamentally from the COG (Children's Oncology Group) protocol in its maintenance chemotherapy regimen, and these protocols are not interchangeable. 1 The St. Jude protocol uses the three-drug combination described above, while COG protocols may use different agents or schedules. Mixing protocols mid-treatment can compromise outcomes and complicate toxicity management. 1

Toxicity Monitoring Requirements

• Vincristine-associated peripheral neuropathy: Monitor neurologic examination at each visit, particularly for distal sensory changes, foot drop, and constipation 1
• Cisplatin-associated ototoxicity: Perform baseline and serial audiometry, as hearing loss occurs in approximately 50% of patients receiving this cumulative cisplatin dose 2, 3
• Hematologic toxicity: Expect neutropenia and thrombocytopenia as the most common dose-limiting toxicities, particularly after cyclophosphamide 2, 4
• Nephrotoxicity: Monitor renal function with creatinine clearance measurements, though severe nephrotoxicity is uncommon with this regimen 2, 3

Clinical Outcomes

The St. Jude protocol was validated in 330 patients with average-risk medulloblastoma, demonstrating 5-year event-free survival of 79% and overall survival of 85% in one cohort. 2 These outcomes are comparable to other prospective studies using similar reduced-dose craniospinal irradiation (23.4-24 Gy) combined with adjuvant chemotherapy. 2

Common Pitfalls to Avoid

• Do not use low-dose CSI (<23.4 Gy): Reducing radiation below 23.4 Gy may compromise disease control 1
• Do not delay radiation therapy: Begin radiation within one month postoperatively to optimize outcomes 1
• Do not switch protocols mid-treatment: The COG and St. Jude maintenance regimens differ significantly in drug selection, dosing, and schedule 1
• Do not cap vincristine at 1 mg: The protocol specifies 1.4 mg/m² with a 2 mg maximum, not the traditional 1 mg cap used in some adult protocols 5, 1

Patient Selection Criteria

Average-risk classification requires meeting all of the following criteria:

• M0 disease (no metastatic spread) 1
• Classic histology (not desmoplastic or large cell/anaplastic) 1
• Gross total resection or near-total resection (>1.5 cm² residual) 1
• Age ≥3 years (radiation is not recommended for patients under 3 years) 1