Optimization of cancer radiotherapy with selective sensitizers.

This study is based on the two-component theory, radiation being considered as composed of a high-LET (alpha) and a low-LET (beta) component. For average tumor-cell parameters (squamous carcinoma) the beta-component will reach a maximum when single doses of 5 to 6 Gy low-LET radiation are given. Here I assume that hypoxic tumor cells can be eliminated by means of selective radiosensitizers. The previously favoured electron-attracting metronidazole and misonidazole have now practically been given up. The enhancement in cell sensitivity was too low and they were too neurotoxic. Newer drugs based on blocking the anaerobic glycolysis (fermentation process) of hypoxic cells seem to be very promising; they have no serious side effects. Special sensitizers supporting the killing of tumor cells with normal oxygen supply could improve radiation therapy. The drug ICRF 159 (resp. 187), "Razoxane" reduces the extrapolation number for proliferating tumor cells. An example shows that therapy with 10 X 6 Gy single doses of high-energy electrons might reduce the number of tumor cells to about 10(-8) with radiation only to nearly 10(-10) if "Razoxane" is given twelve hours before radiation exposures.