To assess the potential value of the 6-day subrenal
capsule (SRC) assay in preclinical evaluation of new drugs using serially xenografted human
tumors as source of
tumor tissue, we studied the response of 31 human
tumor lines (8
malignant melanomas, 12
sarcomas, 9 lung
carcinomas and 2 colon
carcinomas) to relevant standard drugs and to a new imidazotetrazine,
Mitozolomide.
Mitozolomide was found to be the most active
drug tested in 50% of the lung
carcinomas and as active as
CCNU in
melanomas. The activity of the standard anticancer drugs against subrenal grafts closely resembled the patterns seen with the same
tumors in the clinic. In further attempts to validate the procedure, sensitivity profiles of some
tumors were concurrently determined in the subcutaneous (s.c.) nude mouse model. In 11 out of the 12
tumors, the two assays selected the same
drug as being the most active and in most of these
tumors the two procedures gave the same ranking for the different drugs. Also, when the relative sensitivities of a series of
melanoma xenografts to each of two drugs (
DTIC and
CCNU) were tested, the two assays gave the same ranking of the xenografts for each
drug. The concordance between the two assays and the fact that the s.c. nude mouse assay reflects the chemosensitivity of the parent
tumor in patients, suggest that the application of the 6-day SRC assay to xenografted
tumors is a valid and useful procedure permitting rapid preclinical evaluation of new drugs to be carried out at relatively low cost.