JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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New therapeutic possibilities of combined treatment of radiotherapy with oxaliplatin and its liposomal formulation, Lipoxal™, in rectal cancer using xenograft in nude mice.

Anticancer Research 2014 October
AIM: To determine the benefits of irradiation at the time of maximum linking of oxaliplatin to the DNA of tumor cells, and evaluate the potential of its liposomal formulation, Lipoxal™, for chemoradiation therapy.

MATERIALS AND METHODS: Nude mice implanted with human colorectal carcinoma HCT116 cells were injected with oxaliplatin or Lipoxal™. The amount of platinum in tumor, tumoral DNA, normal tissues and blood was measured 4, 24, 48, 72 and 96 h later by inductively coupled plasma mass spectrometry. The effect of concomitant radiotherapy was assessed as tumor growth delay resulting from irradiation 4, 24 and 48 h after drug administration.

RESULTS: While the amount of platinum in the tumor reached a peak at 4 h after injection and declined over time, the concentration of oxaliplatin-DNA adducts reached two maxima observed at 4 h and 48 h after drug administration, a behavior not observed with Lipoxal™. The greatest combined effect was obtained when radiation was given at 48 h after drug injection, resulting in an increase of tumor growth delay by factors of 3.71 and 3.33 for treatments with oxaliplatin and Lipoxal™, respectively.

CONCLUSION: Our results confirm the importance of irradiating a tumor when the concentration of oxaliplatin bound to tumor DNA is maximal. This finding should have a significant impact on the design of more efficient chemoradiation treatment protocols and should be further explored in clinical studies.

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