Higher rates of
glucose usage generally correlate with poor prognosis in several types of malignant tumours. Experimental studies (both in vitro and in vivo) have shown that
2-deoxy-D-glucose (2-DG), a
glucose analog and glycolytic inhibitor, enhances radiation-induced damage selectively in
tumor cells while protecting normal cells, thereby suggesting that 2-DG can be used as a differential radiomodifier to improve the efficacy of
radiotherapy. Clinical trials undertaken to study the feasibility, safety, and validity of this suggested approach will be described. Based on 2-DG-induced radiosensitization observed in primary organ cultures of cerebral
glioma tissues, clinical trials were designed taking into consideration the radiobiology of
gliomas and pharmacokinetics of 2-DG. Phase I/II clinical trials have unequivocally demonstrated that a combination of 2-DG (200-300 mg 2-DG per kg
body weight orally administered after overnight fasting, 20 min before irradiation) with large weekly fractions (5 Gy/fraction) of low-LET
radiotherapy is well tolerated without any acute toxicity or late radiation damage to the normal brain tissue. Nonserious transient side effects similar to
hypoglycemia induced disturbances like
restlessness,
nausea, and
vomiting were observed at the 2-DG doses used. Data from these trials involving more than 100 patients have clearly indicated a moderate increase in the survival, with a significant improvement in the quality of life with clinicopathological evidence of protection of normal brain tissue. A phase III multicentric trial to evaluate the efficacy of the combined treatment is in progress. Directions for future studies are discussed.