vincristine + dactinomycin + cyclophosphamide + irinotecan

The combination of vincristine, dactinomycin, cyclophosphamide, and irinotecan (commonly referred to as the VAC/VI regimen) is an alternating multi-agent chemotherapy protocol primarily utilized in pediatric and young adult oncology for the treatment of intermediate-risk rhabdomyosarcoma (RMS). Developed by the Children's Oncology Group (COG), this regimen alternates cycles of the standard VAC backbone (vincristine, dactinomycin, and cyclophosphamide) with VI (vincristine and irinotecan). The primary therapeutic rationale for incorporating irinotecan and alternating the cycles is to reduce the cumulative dose of cyclophosphamide, thereby mitigating long-term treatment-related toxicities such as gonadotoxicity (infertility) and severe hematologic suppression, while maintaining robust event-free and overall survival rates. Each component of the regimen targets distinct cellular pathways: vincristine inhibits microtubule assembly; dactinomycin intercalates into DNA to block transcription; cyclophosphamide acts as a DNA-alkylating agent; and irinotecan inhibits topoisomerase I to induce lethal double-strand DNA breaks during replication.

Other names

VAC-VIVAC-VI regimenVAC/VIVAC/VI regimenvincristine, dactinomycin, cyclophosphamide, and irinotecan