ABSTRACT
In previous study on cell-cultures, the authors have proved that tinidazole had radiosensitizing properties on hypoxic cells similar to those of metronidazole. The radiosensitizing activity of tinidazole becomes useful in vitro using a concentration of 1 millimol. The purpose of this study was to determine the dose of tinidazole necessary to produce a useful radiosensitizing effect in patients cured by radiotherapy. The pharmacokinetic properties of tinidazole were studied by treating patients with 1.5-3-4.5 g of the drug per day, using single doses for two consecutive days. The plasma concentration was determined by 15 series samples during a period of 48 h. Moreover endotumoural concentrations of tinidazole were studied in a group of patients using high pressure liquid chromatography techniques. The results showed that a dose of 4.5 g of tinidazole was sufficient to reach plasmatic and endotumoural concentrations similar to those which provide a radiosensitizing effect in vitro with an enhancement factor ratio of approximately 1.5. The initial dose and the accumulation factor were also determined in order to maintain the above-mentioned concentrations for a time sufficient to be able to apply multiple daily fractions of radiotherapy. The tolerance of the drug throughout the study was excellent.
Subject(s)
Nitroimidazoles/metabolism , Radiation-Sensitizing Agents/metabolism , Tinidazole/metabolism , Drug Administration Schedule , Humans , Kinetics , Neoplasms/metabolism , Radiation-Sensitizing Agents/administration & dosage , Tinidazole/administration & dosage , Tinidazole/pharmacologyABSTRACT
The prognostic value of CEA for the purposes of postoperative monitoring assessed in 45 patients with cancer of the colon and rectum. Values were obtained 1-36 months after surgery in all operable cases. Means were also evaluated statistically at various follow-up times. In patients who relapsed, values stayed significantly higher for up to 6 months after surgery than in those who did not. Cockran's method showed that the prognostic significance of this difference 6 months after surgery was p less than 0.05.
