826 Cisplatin, carboplatin and irradiation in human ovarian cancer cells

Abstract

Cisplatin (CDDP) and carboplatin (CBDCA) have a similar spectrum of antitumor activity, but a different toxicity. The combination with radiotherapy has been introduced in order to increase therapeutic efficncy. Therefore, we examined whether CDDP and CBDCA interact in the same way with irradiation. Human ovarian cancer cells were continuously exposed to CDDP (0.5, 1, 2.5, 5 μM) or CBDCA (2.5, 5 μM) 16 hand 4 h before and after irradiation with cobalt 60 –y-rays. Survival was determined with the clonogenic assay. Interaction was evaluated by determining the dose enhancement- factors (DEF) and by constructing the isobolograms at different survival levels. The combination of CDDP and irradiation resulted in an independent cell kill. There was no modification of the survival curve. The DEF=0.89–1.08 and in the isoeffect-plot the interaction was additive. Five μM CBDCA before or 4 h after irradiation resulted in supraadditivity. There was an abolition of the shoulder of the dose survival curve. The DEF >1 (1.69–2.68 at 10% survival) and higher at higher survival levels. In the is effect-plot the interactions were supra-additive. The combination with CBDCA 16 h after irradiation (DEF = 0.85-0.96) or at 2.5 μM (DEF = 1) was additive. CBDCA induced enhancement of cell kill for irradiation in certain sequences and from a certain dose on. The combination with CDDP was purely additive. In our study, CBDCA was much better than CDDP as far as interaction with irradiation was concerned.