Use of tritiated nucleotide incorporation for prediction of sensitivity of tumors to cytostatic agents.
Development of a means for prediction of sensitivity or resistance of tumors is of paramount importance for future patient specific tumor therapy. A simple, easily performed short-term in vitro test is described whose basic feature is measurement of changes in incorporation of radioactive nucleic acid precursors into tumor cells after addition of cytostatic agents. In order to determine whether acquired resistance is detectable by means of this in vitro short-term test, resistant animal tumor cell lines were developed to different cytostatic agents. This developed resistance was detectable in the in vitro test system. It was observed that the short-term test could demonstrate cross-resistance, and also development and reversibility of resistance to cytostatics. Further, it is possible to assess the role of proliferative activity of tumors. In a clinical study patients with inoperable ovarian and lung carcinomas (n = 49) were treated by chemotherapy and the results of the treatment compared with the results of the in vitro tests. Tumors which show only a weak response in the in vitro test, also failed to respond to chemotherapy in the clinic. In a cooperative study - conducted by nine different hospitals - results of the short-term test in vitro were compared with results of drug therapy in 151 patients. Of these, 76 were judged resistant and 75 sensitive in the in vitro test. Of these 76 resistant tumors, 56 were clinically progressive (73%), 2 (2%) were in remission and 19 (25%) showed no change. Whilst in the 75 sensitive tumors 18 (24%) progressed clinically, 40 (53%) were in clinical remission and 17 (23%) were unchanged. Therefore if only the definite progression or remission evaluations are compared with the in vitro results 55 of the 57 tumors which were resistant in the test were clinically progressive (96%) and 40 of 58 tumors which were sensitive in the test showed clinical remission (69%). There is also good agreement between the in vitro test results and survival time. Patients whose tumors were resistant in the test generally died sooner than those whose tumors were sensitive. In the studies described - as in other investigations - chemoresistance is shown to be more successfully predicted than chemosensitivity.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001984:Bronchial Neoplasms / Q000188:drug therapy; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D005260:Female; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism*; D009711:Nucleotides; D010051:Ovarian Neoplasms / Q000188:drug therapy; D014316:Tritium
D000970:Antineoplastic Agents; D009711:Nucleotides; D014316:Tritium