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The Olivacine S16020 Enhances the Antitumor Effect of Ionizing Radiation without Increasing Radio-induced Mucositis¹

Unité Propre de Recherche de l’Enseignement Superieur EA 27-10, "Radiosensibilité-Radiocarcinogenèse Humaine," Institut Gustave Roussy, 94805 Villejuif Cedex [L. M., V. F., S. D. R., F. E., J. B.], Institut de Recherches Internationales SERVIER, Division Thérapeutique Cancérologie, Courbevoie 92415 [M-G. P., M. B., C. L.], France

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

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