Cell Culture Drug Resistance Testing (CCDRT) Cell Death Assays:

Misconceptions Versus Objective Data

-Chapter 5-

Correlations Between Assay Results and Patient Survival

The important issue of correlation of assay results with patient survival as well as response is addressed in a recent review by Bosanquet (3). In aggregate, there have been hundreds of published correlations between assay results and patient survival, and the associations are highly positive. When patients are treated with drugs which are not active in these assays, the patients die significantly sooner than when they are treated with drugs which are active in the assays (4-14). Of particular interest are the recently published studies of the MTT assay by Furukawa, et al (Clin Cancer Res 1:305-311,'95), in which dramatic associations between assay results and overall survival and relapse free survival in both colon and stomach cancer are reported in a macrocluster assay measured with the MTT endpoint, and by Veerman, et al (4,11-13,20), which show that not only do assay results predict for overall and relapse-free survival in acute leukemia, but that, on multi-variate analysis, the drug resistance assay results are far more important than any other clinical or laboratory prognostic factor, including all the prognostic factors in widespread use for determining whether "standard" or "intensive" induction therapy should be used. Recently, Bosanquet and co-workers have demonstrated that CLL patients with in vitro fludarabine resistance die much more quickly when treated with fludarabine than when treated with drugs other than fludarabine (Br J Haematol 106:71-7,99). Furthermore, Mason, et al published a clinical correlation analysis indicating the clinical cost-effectiveness of DISC-assay-directed chemotherapy (Int J Technol Assess Health Care 15:173-84,'99). Currently in review for publication in a peer-reviewed journal are data showing survival advantages to patients with stomach and colon cancers when drugs are selected for use in chemotherapy which are active in the assays, compared to patients treated with the physician's choice chemotherapy in these diseases (Hoffman,R. et al, submitted for publication).