The olivacine S16020 enhances the antitumor effect of ionizing radiation without increasing radio-induced mucositis

The combination of a novel topoisomerase II inhibitor, S16020, and ionizing radiation (IR) was investigated with the aim of assessing normal tissue to lerance using a mouse mucosal lip model and antitumor activity in a human c arcinoma (HEP2) cell line. No increase of acute mucosal reactions was seen when combining S16020 with IR as compared with IR alone, Using clonogenic c ell survival assay, a marked enhancement of HEP2 cell killing was found whe n S16020 was combined with irradiation. Additional in vivo combination of S 16020-IR was able to increase markedly the antitumor efficacy as compared w ith S16020 or irradiation alone. Interestingly, the radiosensitization effe ct ill vivo was observed at relatively low and nontoxic concentrations of S 16020, and no dose-effect relationship was found beyond 30 mg/kg. In conclu sion, the combination of IR and S16020 seems promising to enhance antitumor activity without increasing deleterious effect in normal tissues and to pr ovide the basis for a new radio-chemotherapy combination.