Evolution of chemotherapy treatment for Wilms tumor
Chemotherapy was introduced for the treatment of pediatric solid tumors just over five decades ago. Prior to that time, surgery and radiotherapy were the only effective treatment modalities. Actinomycin D was the first agent shown to be effective for treatment of Wilms tumor. Actinomycin, derived from Streptomyces and discovered in 1940, was initially thought to be useful as an antibiotic. The drug was noted to be too toxic causing myelosuppression.
Actinomycin D was noted to have anticancer activity in animal models by Dr. Sidney Farber, a pathologist at Harvard. Farber had previously reported the successful treatment of acute leukemia in children with antifolate drugs. They noted that actinomycin D could eliminate some metastases in children with advanced Wilms tumor. More importantly, they demonstrated improved survival in children when the drug was given immediately after nephrectomy. This was the beginning of routine adjuvant therapy for the treatment of solid neoplasms in children. Dr. Dan D’Angio, a radiation oncologist and one of the founders of the National Wilms Tumor Study, working with Dr. Farber reported that the effects of radiotherapy could be potentiated by administration of actinomycin D.
Vincristine, a plant alkaloid derived from the periwinkle plant, was the second drug shown to marked activity in children with Wilms tumor. Dr. Wataru Sutow, an oncologist at M. D. Anderson Cancer Center, showed that this drug could rapidly reduce the size of metastases and the primary tumor with little myelosuppression. These two drugs, dactinomycin and vincristine, were later studied as a combination therapy in the first randomized trial for the treatment of Wilms tumor conducted by the National Wilms Tumor Study.