Enhanced response of human head and neck cancer xenograft tumors to cisplatin combined with 2-deoxy-D-glucose correlates with increased 18F-FDG uptake as determined by PET imaging.
OBJECTIVE
To determine whether the response of human head and neck cancer xenografts to cisplatin (CIS) could be enhanced with 2-deoxy-D-glucose (2DG); whether 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) uptake correlated with responses to this drug combination; and whether 2DG would enhance CIS-induced radiosensitization.


METHODS
Clonogenic survival responses to CIS + 2DG were determined in FaDu and Cal-27 cells and reduced/oxidized glutathione levels were monitored as parameters indicative of oxidative stress. The efficacy of CIS + 2DG was determined in FaDu and Cal-27 xenografts, and FDG uptake was determined by using positron emission tomography.


RESULTS
Use of CIS + 2DG enhanced cell killing of FaDu and Cal-27 cells compared with either drug alone while increasing the percentage of oxidized glutathione in vitro. Use of CIS + 2DG inhibited FaDu and Cal-27 tumor growth and increased disease-free survival compared with either drug alone. The Cal-27 tumors showed greater pretreatment FDG uptake and increased disease-free survival when treated with 2DG + CIS relative to FaDu tumors. Treatment with 2DG enhanced CIS-induced radiosensitization in FaDu tumor cells grown in vitro and in vivo and resulted in apparent cures in 50% of tumors.


CONCLUSIONS
These results show the enhanced therapeutic efficacy of CIS + 2DG in human head and neck cancer cells in vitro and in vivo compared with either drug alone, as well as the potential for FDG uptake to predict tumor sensitivity to 2DG + CIS. These findings provide a strong rationale for evaluating 2DG + CIS in combined-modality head and neck cancer therapy with radiation in a clinical setting.
Simons
Andrean L
AL
Department of Radiation Oncology, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
Fath
Melissa A
MA
Mattson
David M
DM
Smith
Brian J
BJ
Walsh
Susan A
SA
Graham
Michael M
MM
Hichwa
Richard D
RD
Buatti
John M
JM
Dornfeld
Ken
K
Spitz
Douglas R
DR
D000704:Analysis of Variance; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D002945:Cisplatin / Q000627:therapeutic use*; D003847:Deoxyglucose / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005978:Glutathione / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018384:Oxidative Stress; D049268:Positron-Emission Tomography; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014183:Transplantation, Heterologous
D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D005978:Glutathione; D002945:Cisplatin