INVIVO CONTROL OF TUMOR-GROWTH BY LONIDAMINE AND RADIATIONS - INFLUENCE OF THE TIMING AND SEQUENCE OF DRUG ADMINISTRATION AND IRRADIATION TREATMENT

It has been well established that Lonidamine (LND), [1,(2,4 dichlorobenzyl)-1H-indazol-3-carboxylic acid], affects tumor growth and enhances the effect of X-ray both in vitro and in vivo. Nevertheless, difficulties arise if the available experimental data should be utilized to design clinical trials since schedules, routes of administration as well as dosages greatly differ from those currently employed in the clinic. With the aim to overcome these difficulties, experiments with modalities similar to those employed in the current clinical practice have been undertaken to evaluate: (i) the influence of the LND dosage on the antitumor effect; (ii) the time lenght of its administration for the optimal effect; (iii) the best schedule of treatment when LND is associated with radiations. The results may be summarized as follows: (i) antitumor effectiveness of LND, in terms of growth delay, increases with LND dosage. Moreover, the drug administered from the day of transplant significantly decreases the tumor takes. (ii) to exert the antineoplastic effect LND must be administered continuosly because if the treatment is interrupted the tumor regrows like an untreated one. (iii) the maximal response of the association X-ray-LND is elicited when the drug is given after irradiation treatment.