IMPORTANCE OF THE IRRADIATION TIMING WITHIN A CHEMORADIOTHERAPY SEQUENCE INCLUDING CISPLATIN AND 5-FU-FOLINIC ACID - EXPERIMENTAL RESULTS

The objective of the present in vitro study was to determine an optima l timing of the irradiation in the combination cisplatin (CDDP) and 5- fluorouracil-folinic-acid (5-FU-FA) allowing a maximal cytotoxic effec t on a human cell line derived from a head and neck carcinoma (CAL 27 cells). The various tested chemoradiotherapy sequences were applied in parallel to human keratinocytes in culture (SVK 14 cells). This was d one in order to define the best sequence allowing the achievement of a n optimal selectivity of the cytotoxic effects. The drug sequence was: CDDP over 2 h then fresh medium was added including the tandem 5-FU-d ,I FA applied 6 h after CDDP, for 5 days. Irradiation was applied only once and at various times within the drug sequence. The cytotoxicity effects of the different chemoradiotherapy combinations were assessed by the MTT semi-automated test. The part taken by the 5-FU-FA combinat ions in the overall cytotoxicity was examined; an effect was apparent on CAL 27 cells only. The evolution of the radiation effect (RE = cell survival after drugs/cell survival after drugs plus irradiation) was analysed as a function of the different times of irradiation within th e given drug sequence. Clearly, the RE values were dependent upon time at which the radiation dose in the chemoradiotherapy regimen was admi nistered. For CAL 27 cells, irradiation effects were maximal at the fi rst irradiation time tested after the end of the CDDP exposure (i.e. t = 3.5 h). In contrast, this optimal chemoradiotherapy timing for bett er cytotoxicity on CAL 27 cells did not correspond to that of SVK 14 c ells. Consequently, it was possible to establish that the best time fo r the selectivity index was located shortly after the CDDP exposure.