Five-chlorodeoxycytidine and biomodulators of its metabolism result in fifty to eighty percent cures of advanced EMT-6 tumors when used with fractionated radiation
- Univ. of Miami School of Medicine, FL (United States)
The purpose of this investigation was to extend our findings in previous radiation and biochemical studies with five rodent tumors, in which we used one and occasionally two or three irradiations. The extent of control of the EMT-6 mammary adenocarcinoma was determined using fractionated radiation (12 irradiations) over a 3-week period using the radiosensitizer 5-chloro-2{prime}-deoxycytidine (CldC) and biomodulators of its metabolism. Drug and radiation treatments overlapped for 3 weeks. Fifty to 80% cures (usually 70%) were obtained with no apparent morbidity and the same moderate weight loss that occurs with radiation alone. An apparent threefold dose increase effect was obtained with the end point: {open_quotes}days to reach 4 times initial tumor volume.{close_quotes} Increasing the radiation dose threefold (without drugs) resulted in four out of five deaths; increasing the dose twofold (without drugs) resulted in extensive weight loss and hair loss in the entire ventral area and no cures. Increasing the dose of drugs or radiation 1.5-fold, in the complete protocol, did not result in increased morbidity. Comparative studies with Iododeoxyuridine demonstrate the heightened efficacy of CldC. One cannot achieve the same results obtained with CldC and the modulators by merely increasing the dose of radiation. There is a significant window of safety in this approach. The evidence we have obtained with EMT-6, the fifth rodent tumor we have studied with CldC, as well as the demonstrated and proposed reasons for its superior efficacy over 5-Iododeoxyuridine (and 5-Bromodeoxyuridine), drugs in current use, indicate that CldC will allow more aggressive treatment of human tumors with radiation than is now feasible. 50 refs., 2 figs., 4 tabs.
- OSTI ID:
- 433189
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 32, Issue 4; Other Information: PBD: 15 Jul 1995
- Country of Publication:
- United States
- Language:
- English
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