A phase I trial of tocoferol monoglucoside in patients undergoing hemi-body radiation.

PURPOSE: To evaluate Tocoferol monoglucoside (TMG), a water soluble vit. E. in a phase I trial, as a radiation protector in those undergoing hemi-body radiation for disseminated disease. MATERIALS AND METHODS: Patients scheduled to receive modified hemi-body radiation were accrued for the study. Patients not only had disseminated skeletal disease but, were heavily pretreated Seven patients were accrued for the study. Patients received 1 and 2 gms of TMG. 30-40 minutes before hemibody radiation. A dose of 600 cGy was delivered on telecobalt equipment at mid plane. Immediate Toxicities were evaluated as well as response to pain. RESULTS: All the seven patients underwent radiation uneventfully. There was no drug related toxicity. Pain relief was adequate. CONCLUSION: Tocoferol monoglucoside an effective antioxidant with no significant acute toxicity, when administered in a dose of 1 or 2 gms per oral route. TMG being water-soluble can have global antioxidant and radio protective effects. This needs further clinical evaluation.

Sanazole as a sensitizer of hypoxic cells with radical radiation in the treatment of advanced cancer of cervix an Indian experience.

AK-2123, is a nitrotriazole with a potential to sensitize hypoxic tissue to radiation. Cancer of cervix in advanced stages are predominantly treated with radiation. These are the tumours which harbour a large hypoxic core. This is an Indian experience of the multicentric trial. Patients were randomized to control and AK-2123 arm. 49 patients were randomized to each group. Patients received external radiation with telecobalt to a dose of 50 Gy in five weeks. Those in the study arm received 600 mg/m2, on alternate days. The patients were further treated with intracavitory radiation a dose of 20 Gy. The total dose of 70 Gy was achieved. Patients in the study arm had a complete response of 71.43% (35 of 49) while only 21 of 49 (42.86%) responded in the control group. The overall survival at two years was 72.2% for the study group and 32.43% for control. Neuropathy, a drug related toxicity was transient except, in one patient, which has persisted. AK-2123, has shown significant radiation sensitizing potential.

Effect of a water soluble derivative of alpha-tocopherol on radiation response of Saccharomyces cerevisiae.

The radioprotection conferred by a highly water soluble glucose derivative of alpha-tocopherol, namely, 2-(alpha-D-glucopyranosyl) methyl-2,5,7,8-tetramethylchroman-6-ol (TMG) in Saccharomyces cerevisiae was studied. Cells grown in standard YEPD-agar medium and irradiated in the presence of TMG showed a concentration dependent higher survival up to 10 mM of TMG in comparison to cells irradiated in distilled water. Treatment of TMG to cells given either before or immediately after irradiation but not during irradiation, had no effect on their radiation response. S. cerevisiae strain LP1383 (rad52) which is defective in recombination repair showed enhanced radioresistance only when subjected to irradiation in presence of TMG. Cells of rad52 strain grown in the medium containing TMG showed a radiation response similar to that of cells grown in the medium without TMG. The nature of TMG dependent enhanced radioresistance was studied by scoring the mutations in the strain D-7, which behaved like wild type strain in complete medium, at trp and ilv loci. Our study indicated that TMG confers radioresistance in S. cerevisiae possibly by two mechanisms viz. (i), by eliminating radiation induced reactive free radicals when the irradiation is carried out in the presence of TMG and (ii), by activating an error prone repair process involving RAD52 gene, when the cells are grown in the medium containing TMG.