MODIFYING EFFECT OF ORGANOCOBALT COMPLEXES ON THE TUMOR RESPONSE TO ANTICANCER TREATMENTS

A new type of agents are proposed for combined cancer therapy. They ar e organocobalt (III) chelates containing a sigma-bounded organyl group and a mixed tridentate ligand derived from a Schiff base. These compl exes generate free radicals due to the action of protons in physiologi cal ranges of pH and temperature, and hence are conceivably capable of selectively attacking a malignant neoplasm that is slightly acidic an d can be made even more so by introducing some means intensifying glyc olysis. An in vivo examination was performed using transplanted mt tum ours (Guerin and Walker 256 carcinomas, Sarcoma 45). The modifying eff ect of one of these complexes on the tumour response to cis-DDP, radia tion and/or local hyperthermia was tested by means of tumour growth de lay assay and local tumour control The potentiating effect of the comp lex was maximal when it was administered 60-90 minutes prior to other agents (cisDDP, X-irradiation, heat). The enhancement ratio was found to be ca. 2.0-4.0 for cisDDP and 2.0 for radiation. In conclusion, in our tumour models an increase of the antitumour effect was obtained fo r conventional antitumour agents when they were supplemented with orga nocobalt complex. it can be hypothesised that DNA in tumour cells may be considered to be the main target for organocobalt complexes.