Adjuvant Chemotherapy Protocol for Standard-Risk Medulloblastoma
Recommended Protocol
For this 4-year-old boy with standard-risk medulloblastoma who has completed chemoradiotherapy, implement the St. Jude maintenance chemotherapy protocol consisting of 6 cycles of vincristine, cisplatin, and cyclophosphamide administered every 4 weeks. 1, 2
Patient-Specific Dosing Calculations
Body Surface Area (BSA)
- Weight: 12 kg
- Height: 99 cm
- Calculated BSA: Approximately 0.54 m² (using standard pediatric BSA formulas)
Chemotherapy Doses Per Cycle
Vincristine:
- Dose: 1.5 mg/m² IV push on Day 1,8, and 15 of each cycle 2
- Patient dose: 0.81 mg per dose (0.54 m² × 1.5 mg/m²)
- Maximum cap: 2 mg per dose 2
- Critical note: Do NOT cap vincristine at 1 mg; use the calculated dose up to 2 mg maximum 2
Cisplatin:
- Dose: 70 mg/m² IV infusion on Day 1 of each cycle 2
- Patient dose: 37.8 mg (0.54 m² × 70 mg/m²)
- Administration: Infuse over 6 hours with aggressive pre- and post-hydration 2
Cyclophosphamide:
- Dose: 1000 mg/m² IV infusion on Day 1 and Day 2 of each cycle 2
- Patient dose: 540 mg per day × 2 days = 1080 mg total per cycle
- Administration: Infuse over 1 hour with mesna uroprotection 2
Treatment Schedule
Cycle Structure
- Total cycles: 6 cycles 1, 2
- Cycle length: Every 4 weeks (28 days) 1, 2
- Total duration: Approximately 24 weeks (6 months)
Day-by-Day Administration
- Day 1: Vincristine + Cisplatin + Cyclophosphamide
- Day 2: Cyclophosphamide only
- Day 8: Vincristine only
- Day 15: Vincristine only
- Days 16-28: Recovery period before next cycle 2
Critical Supportive Care Measures
Hydration Protocol for Cisplatin
- Pre-hydration: Normal saline at 200 mL/m²/hour for 2 hours before cisplatin 2
- During infusion: Continue hydration throughout 6-hour cisplatin infusion
- Post-hydration: Normal saline at 200 mL/m²/hour for 2 hours after cisplatin
- Maintain urine output: >100 mL/m²/hour during and after cisplatin administration
Mesna Protocol for Cyclophosphamide
- Dose: Mesna at 20% of cyclophosphamide dose given at 0,4, and 8 hours after cyclophosphamide
- Patient-specific: 108 mg mesna per dose (20% of 540 mg)
- Purpose: Prevent hemorrhagic cystitis
Antiemetic Prophylaxis
- 5-HT3 antagonist (ondansetron 0.15 mg/kg IV) before chemotherapy
- Dexamethasone 4-8 mg IV before highly emetogenic agents
- Consider aprepitant for breakthrough nausea
Mandatory Toxicity Monitoring
Vincristine-Associated Neuropathy
- Assess before each dose: Deep tendon reflexes, gait, constipation, jaw pain 1, 2
- Hold vincristine if: Grade 3-4 peripheral neuropathy develops
- Common manifestations: Foot drop, wrist drop, severe constipation, paresthesias
- Prophylaxis: Stool softeners and bowel regimen throughout treatment
Cisplatin-Associated Ototoxicity
- Baseline audiometry: Before starting maintenance chemotherapy 1, 2
- Serial audiograms: Before cycles 3 and 5, and at end of treatment
- High-frequency hearing loss: Most common toxicity, may be irreversible
- Consider dose modification: If significant hearing loss develops (>20 dB at speech frequencies)
Hematologic Monitoring
- CBC with differential: Before each cycle and on Days 8 and 15 3
- Delay cycle if: ANC <1000/μL or platelets <75,000/μL
- Growth factor support: Consider G-CSF if prolonged neutropenia occurs
Renal Function Monitoring
- Before each cycle: Serum creatinine, BUN, electrolytes (especially magnesium) 3
- Cisplatin nephrotoxicity: Monitor for rising creatinine, hypomagnesemia
- Dose modification: Reduce cisplatin by 50% if creatinine clearance 40-60 mL/min
Protocol-Specific Considerations
Why St. Jude Protocol Over COG Protocol
- Both protocols are acceptable for standard-risk medulloblastoma 1, 2
- St. Jude uses: Vincristine + cisplatin + cyclophosphamide 1, 2
- COG alternates: Between cisplatin/lomustine/vincristine and cisplatin/cyclophosphamide/vincristine 1
- Critical warning: These protocols are NOT interchangeable; do not mix regimens mid-treatment 1, 2
Evidence Supporting This Approach
- St. Jude trial (n=330): Demonstrated comparable outcomes to other prospective studies using this exact regimen 1, 2
- 5-year outcomes: Event-free survival and overall survival rates support this as standard of care 1
- Smaller study (n=33): Using reduced-dose CSI with cisplatin/vincristine/cyclophosphamide showed 79% EFS and 85% OS at 5 years 3
Common Pitfalls to Avoid
Dosing Errors
- Never cap vincristine at 1 mg in pediatric patients; use 1.5 mg/m² up to 2 mg maximum 2
- Do not reduce cyclophosphamide dose without clear indication; cumulative dose intensity matters
- Maintain cycle timing: Delays beyond 1 week may compromise efficacy
Protocol Mixing
- Do not switch between St. Jude and COG protocols mid-treatment 1, 2
- Do not substitute lomustine for cyclophosphamide or vice versa
- Follow one protocol completely through all 6 cycles
Inadequate Supportive Care
- Insufficient hydration with cisplatin increases nephrotoxicity risk
- Omitting mesna with cyclophosphamide risks hemorrhagic cystitis
- Inadequate antiemetic prophylaxis leads to poor quality of life and treatment delays
Monitoring Failures
- Missing ototoxicity early: Irreversible hearing loss impacts quality of life significantly 1
- Ignoring neuropathy: Can lead to permanent disability if vincristine continued
- Inadequate CBC monitoring: Risks severe infection or bleeding complications
Quality of Life Considerations
Expected Toxicities
- Hematologic toxicity: Most common side effect, generally manageable 3
- Nausea/vomiting: Expected but controllable with modern antiemetics 3
- Ototoxicity: May be permanent; counsel family about hearing aids if needed 1
- Peripheral neuropathy: Usually reversible after vincristine completion 1
Neurocognitive Outcomes
- Minimal IQ decline: Only 28.6% showed insignificant IQ decline in one study using this regimen 3
- Better than radiation alone: Chemotherapy allows for reduced radiation doses, preserving cognition
- Long-term monitoring: Annual neurocognitive assessments recommended
Fertility Preservation
- Pre-treatment counseling: Should have been completed before initial therapy 4
- Cyclophosphamide risk: Moderate gonadotoxicity; sperm banking not applicable at age 4
- Future considerations: Discuss fertility preservation options when patient reaches adolescence
Treatment Modifications
Dose Reductions
- Cisplatin: Reduce by 50% if creatinine clearance 40-60 mL/min; omit if <40 mL/min
- Vincristine: Hold for Grade 3-4 neuropathy; resume at 50% dose when improved to Grade 1
- Cyclophosphamide: Reduce by 25% for Grade 4 hematologic toxicity lasting >7 days
Cycle Delays
- ANC <1000/μL or platelets <75,000/μL: Delay cycle by 1 week, recheck counts
- Active infection: Delay until resolved and ANC recovered
- Maximum delay: Do not delay >2 weeks without oncology team discussion