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.