HD-CCV: High-Dose Cyclophosphamide, Irinotecan, and Vincristine
HD-CCV is a salvage chemotherapy regimen consisting of high-dose cyclophosphamide (140 mg/kg), irinotecan (250 mg/m²), and vincristine, primarily used for treating refractory or relapsed neuroblastoma that has not responded adequately to standard induction therapy. 1
Regimen Composition and Administration
- Cyclophosphamide is administered at 140 mg/kg over 2 days 1, 2
- Irinotecan (CPT-11) is given at 250 mg/m² 1
- Vincristine dosing follows standard protocols 1
- The regimen is typically administered on an outpatient basis, making it more convenient than many intensive salvage protocols 1
Clinical Indications and Patient Selection
Primary Use: Neuroblastoma
- Most effective when administered ≤9 months from diagnosis, achieving responses in 43% of patients (12/28) compared to only 10% (1/10) when given >10 months from diagnosis 1
- Designed specifically for neuroblastoma that has responded incompletely to induction therapy but has never progressed 1
- Can be used as initial salvage after topotecan-containing induction regimens 1
Response Rates by Clinical Subset
- Primary refractory neuroblastoma in children: 45% combined response rate (major responses plus mixed responses) 3
- Secondary refractory neuroblastoma: 71% combined response rate 3
- First disease recurrence: 80% combined response rate 3
- Progressive disease while on therapy: Only 8% response rate 3
Important Clinical Considerations
Age-Related Efficacy
HD-CCV shows dramatically different efficacy between children and adolescents/adults. All 10 adolescents/adults treated for primary refractory neuroblastoma had no response, which was significantly inferior to the 45% response rate in children (P = 0.008) 3. This represents a critical selection criterion.
Toxicity Profile
- Grade 4 myelosuppression is the most common toxicity 1
- Grade 2 diarrhea occurs frequently, likely related to the irinotecan component 1
- Toxicities are generally manageable in the outpatient setting 1
Cross-Resistance Patterns
- HD-CCV produced responses (2 partial, 3 mixed) in all 5 patients previously treated with irinotecan/temozolomide, suggesting lack of complete cross-resistance 1
- However, all 6 patients treated post-HD-CCV with irinotecan/temozolomide had no response, indicating that HD-CCV may induce resistance to subsequent irinotecan-based regimens 1
Outcomes and Survival Data
- Progression-free survival: 64% (±8%) at 24 months 1
- Complete response rate: 5/38 patients (13%) achieved complete remission 1
- 20 patients remained progression-free at 2+ to 36+ months (median 16+ months) 1
- 10 patients achieved first complete remission lasting 9+ to 36+ months (median 16+ months) 1
Integration with Multimodal Therapy
Post-HD-CCV treatments that have been successfully integrated include:
Key Clinical Pitfalls
Avoid using HD-CCV in adolescents/adults with primary refractory neuroblastoma, as response rates are essentially zero compared to children 3. Do not use HD-CCV for progressive disease while on active therapy, as response rates drop to 8% 3. Timing matters critically—administer within 9 months of diagnosis for optimal efficacy 1.