Studies on Combined Experimental Antitumor Drug Therapy. An Attempt to Overcoming the Natural Drug Resistance

ABSTRACT

Modern drug therapy of cancer patients is mainly combined. The possibilities of using a new non-myelo- and non-immuno-suppressive antitumor drug of natural origin, Thaliblastine (TBL), in combination with the clinically applied cytostatics, has been studied systematically in the Lab. of Oncopharmacology, Nat. Oncological Center, Sofia. The influence of semi-synthetic Vinca rosea alkaloid vinorelbine (VRB) (Navelbine, Pierre Fabre Medicament, France) on the antiproliferative activity of TBL has been studied in vitro on permanent human tumor cell line HeLa, by using the semi-automatetd microcolorimetric MTT test of Mosmann. VRB in sub-cytotoxic concentrations enhanced the antiproliferative activity of TBL. In series of in vivo studies the influence of TBL combined with VRB on the life span of BDF1 hybrid mice with ascitic lymphoid leukaemia L1210 has been investigated. TBL did not show any own antitumor activity on leukaemia L1210 (T/C.100 < 125.0%). VRB manifested its own antitumor activity (T/C.100 = 145.8%). Any enhancement of antitumor activity at the combined treatment with both drugs has not been found. In the higher doses at the same protocol “toxic” values of the criterion T/C.100 have been observed. In conclusion, in the clinical practice the combined treatment with TBL and VRB is not recommended in view of considerable increasing of the common toxicity at used protocol. Combined treatment failed to overcome the natural drug resistance ofL1210 leukemia to TBL. Further experiments in this field are in progress.