What is ACD Chemotherapy for Ewing Sarcoma?
ACD is not a standard chemotherapy regimen for Ewing sarcoma—the correct terminology is VACD (vincristine, actinomycin-D/dactinomycin, cyclophosphamide, and doxorubicin), which was a historical 4-drug regimen that has been superseded by more effective modern protocols. 1
Historical Context of VACD
The VACD regimen was evaluated in the Intergroup Ewing's Sarcoma Studies (IESS-I and IESS-II) and demonstrated superiority over the 3-drug VAC regimen (vincristine, actinomycin, cyclophosphamide), achieving 60% relapse-free survival versus 24% with VAC. 1
However, VACD alone is now considered inferior and should not be used as monotherapy because subsequent trials demonstrated significantly better outcomes when ifosfamide and etoposide were added. 1
Why VACD Alone is Obsolete
The Pediatric Oncology Group-Children's Cancer Group study (INT-0091) definitively showed that VACD alternating with ifosfamide and etoposide (VACD-IE) achieved:
- 5-year event-free survival of 69% versus 54% with VACD alone (P=0.005) 1
- 5-year overall survival of 72% versus 61% with VACD alone (P=0.01) 1
- Local failure rate of 11% versus 30% with VACD alone 1
Current Standard of Care
The modern standard regimen is VDC/IE (vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide) given on an interval-compressed every-2-week schedule, which has replaced VACD-based therapy. 1, 2, 3
Key Components of Modern Therapy:
- VDC cycles: Vincristine 2 mg/m², doxorubicin 75 mg/m², cyclophosphamide 1.2 g/m² 2
- IE cycles: Ifosfamide 9 g/m², etoposide 500 mg/m² 2
- Schedule: Every 2 weeks (interval-compressed) with filgrastim support, which achieved 73% 5-year event-free survival versus 65% with every-3-week dosing 2
- Duration: 14 total cycles over approximately 28-30 weeks 2, 3
European Alternative:
The EURO EWING 2012 trial demonstrated that the US regimen (VDC/IE) was superior to the European VIDE regimen, with 3-year event-free survival of 67% versus 61%, less toxicity, and shorter treatment duration. 3
Clinical Implications
If you encounter "ACD" in clinical practice, clarify whether the intended regimen is:
- VACD (the obsolete 4-drug regimen that should not be used alone) 1
- VAC (the even older 3-drug regimen without doxorubicin, which is definitively inferior) 1
- Modern VDC/IE (the current standard that should be used) 1, 2, 3
The actinomycin-D component is still used in some consolidation phases (such as VAI or VAC consolidation in European protocols), but never as part of primary induction therapy without the addition of ifosfamide and etoposide. 1, 3