Combining Cisplatin with Different Radiation Qualities-Interpretation of Cytotoxic Effects In Vitro by Isobolographic Analysis.

BACKGROUND

The combination of platinum-containing cytostatic drugs with different radiation qualities has been studied for years. Despite their massive side effects, these drugs still belong to the therapeutic portfolio in cancer treatment. To overcome the disadvantages of cisplatin, our study investigated the cytotoxic effects of combining radionuclides with cisplatin.

METHODS

FaDu cells were treated with cisplatin (concentration ≈ 2 µM) and additionally irradiated after two hours with the alpha-emitter Ra, the beta-emitter Re as well as external X-rays using dose ranges of 2-6 Gy. Cell survival was followed by colony formation assays and plotted against cisplatin concentration and radiation dose. The results were interpreted by isobolograms.

RESULTS

Isobolographic analyses revealed a supra-additive cytotoxic effect for the combination of cisplatin and Ra. A sub-additive effect was observed for the combination of cisplatin and Re, whereas a protective effect was found for the combination with X-rays.

CONCLUSIONS

The combination of cisplatin and Ra may have the potential to create a successfully working therapy scheme for various therapy approaches, whereas the combination with Re as well as single-dose X-ray treatment did not lead to a detectable radiosensitizing effect. Thus, the combination with alpha-emitters might be advantageous and, therefore, should be followed in future studies when combined with cytostatic drugs.