The development of VAC chemotherapy in rhabdomyosarcoma: what does one do for an encore?

The establishment of the Intergroup Rhabdomyosarcoma Study (IRS) Committee in 1972 by three extant American pediatric cooperative groups initiated five generations of studies in the multidisciplinary treatment of soft-tissue sarcomas. Taking the lead from the use of vincristine, actinomycin-D, and cyclophosphamide (VAC) by Dr. Ruth Heyn, Dr. Harold Mauer and colleagues developed a more robust VAC as well as three similar drug regimens with hematopoietic growth factor support, which, in the context of surgery with or without radiotherapy, achieved a 3-year failure-free survival rate of 83% (IRS-IV) in nonmetastatic embryonal rhabdomyosarcoma. This review documents the development of VAC and some of the new directions currently being pursued by the Children's Oncology Group Soft Tissue Committee.