Synergism in Concomitant Chemoradiotherapy of Cisplatin and Oxaliplatin and their Liposomal Formulation in the Human Colorectal Cancer HCT116 Model

Background: We choose to test the effect of associating chemo-radiotherapy at 8 h (the highest level of DNA-platinum) and 48 h (the lower level of DNA-platinum) to clarify if irradiation at the maximum DNA-platinum concentration could improve the synergism. Materials and Methods: Growth inhibition of the human colorectal cancer cell line HCT116 treated with cisplatin, oxaliplatin, Lipoplatin™ and Lipoxal™ plus gamma-radiation was determined by a colony formation assay. The synergism was evaluated using the combination index method. Results: For 8 h and 48 h exposure to cisplatin or Lipoplatin™, followed by irradiation, drug concentrations higher than IC 50 were found to be synergistic, while a lower than IC 50 concentration was antagonistic. For oxaliplatin, exposure to a concentration above IC 50 for 8 h was synergistic, while the exposure to oxaliplatin (at any concentrations) for 48 h was antagonistic. Lipoxal™ significantly improved synergism compared to its parent drugs. All tested platinum drugs sensitize radiation- treated HCT116 cells by inducing G 2 phase. Conclusion: The difference of drug concentrations and the time interval between drug administration and radiotherapy could give different results in chemoradiation therapy. The addition of chemotherapy to radiotherapy is expected to improve treatment outcome of numerous malignant diseases. This is evident in head and neck, lung, anal and rectal cancers (1-3), but for some other cancers the benefit of such association is less clear (ex. pancreatic cancer) (4). Some chemotherapeutic agents (as well as other drugs) have also been proposed to enhance the efficacy of radiotherapy, in