Interactions entre le carboplatine, le cisplatine et les rayonnements ionisants dans une lignée cellulaire humaine de cancer ovarien

Scalliet, Pierre [UCL] De Pooter, C. Hellemans, P.W.J. De Bruijn, E.A. Van Oosterom, A.T.

© Elsevier, Aim of the study. - Cisplatin (CDDP) and radiotherapy are freqi.ently used concomitantly in the treatment of various malignant conditions. Because of its toxicity, cisplatin tends to be replaced by carboplatin (CBDCA) in several indications. Available data regarding the combined effects of cisplatin and carboplatin with ionising radiation are contradictory. Materials and methods. - Various concentrations of cisplatin and carboplatin and various timing of association with radiation have been tested in vitro in a human ovarian cancer cell line. The parental cell line (AOvC-0) and a cisplatin-resistant stable subline (AOvC-CDDP/0) (De Pooler et al., Cane Res, 1991 ) were exposed to carboplatin (2.5, 5 and 10 M) and to CDDP (1, 2.5 and 5 M), 16h and 4h before and 4h and 16h after irradiation, respectively. Cell survival was evaluated by a classical clonogenic assay. Results. - Exposure of AOvC-0 to 5 M CBDCA and of AOvC-CDDP/0 to 10 M CBDCA, before or shortly after radiation exposure, increased cell lethality in a clear supra-additive way, with the highest DEF in the shoulder region of the survival curve and at radiation doses relevant to clinical radiotherapy. In the sensitive eel! line, 5 M carboplatin resulted in an additional lethality equivalent to 4.5 Gy ; in the resistant cells, 10 M carboplatin was equivalent to 3.6 Gy. Replacing carboplatin by cisplatin in an identical set-up demonstrated exclusively simple additivity (DEF = 1). Conclusion. - These data suggest that carboplatin and cisplatin delivered at equitoxic doses interact with radiation in a different way and that, in the present set-up, only carboplatin enhanced the effects of radiation. Carboplatin might consequently be a better candidate than cisplatin in some concomitant combinations with radiotherapy. © 1999, Elsevier,.