Application of an in vitro antimetabolic assay to human germ cell testicular tumors for the preclinical evaluation of drug sensitivity.
An in vitro assay, which evaluates the effect of drugs on labeled nucleotide precursor incorporation 3H-thymidine and 3H-uridine after 3 hours of in vitro treatment, was applied to human germ cell testicular tumors. The assay was feasible on 78% of the 259 tumors, and the results were evaluable in 95% of these, which shows the good potential of its clinical application. In vitro response rates to conventional agents were comparable to clinical response rates reported in the literature for monochemotherapy regimens, thus demonstrating the accuracy of the assay in reproducing the sensitivity of the tumor type. The specificity of the assay in predicting drug sensitivity of individual tumors was investigated on 28 lesions from 24 patients who had residual disease after surgery. A significant correlation was found between in vitro and clinical sensitivity to the same drugs (P = 0.026), with an overall agreement of 92% when tumor metastases were tested in vitro. In contrast, no significant correlation, and a poor agreement (62%) was found when the primary tumor was tested.
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D003114:Colony-Forming Units Assay; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014410:Tumor Stem Cell Assay
D000964:Antimetabolites, Antineoplastic