The Radiation Oncology Branch has demonstrated that IUdR, given by continuous intravenous infusion for 24 hours a day for up to 14 days, can function as an effective radiosensitizer in high-grade primary brain tumors, and other poorly responsive tumors. The treatment protocol involves two separate two-week infusions of IUdR combined with twice daily radiation therapy. The purpose of this study was to combine IUdR with modest doses of FUdR in an attempt to increase the uptake of IUdR within tumor cells by means of blocking de novo thymidine synthesis. The reasoning was that IUdR competes with thymidine in dividing cells, and thus by blocking thymidine synthesis, IUdR can be expected to be more effective. Thirty-five patients were treated with a variety of diagnoses, but mostly sarcomas and gliomas. Escalating doses of FUdR were given. along with escalating doses of IUdR. There was a marked increase in toxicity, not only in terms of metabolic toxicity, but also abnormal liver function tests, and severe mucositis and diarrhea. The study was terminated after 35 patients. It did demonstrate that FUdR did have the capacity to increase the proportion of incorporation of IUdR; however, the FUdR infusion required a decrease in the total IUdR used, and appeared to be much more toxic.
