The subrenal capsule technique proved effective in demonstrating that the growth of human tumors in normal, immunocompetent animals for 6 days was quantifiable in ocular micrometer units. Positive growth was demonstrable not only with human tumors that had been established in serial transplantation in athymic nude mouse hosts, but also with primary surgical explants. Growth rates of transplantation-established xenograft systems were similar whether implanted in athymic nude or in normal immunocompetent animals indicating that the 6-day time-frame successfully evades growth inhibitory effects of immunologic origin. Immunosuppression with a single dose of cyclophosphamide did not appear to affect growth rate, but permitted the tumors to grow larger extending the time to reach peak size. Significantly, xenografts of primary surgical explants showed positive growth more frequently in 6 days (82%) in the immunocompetent animal than in 11 days (30%) in the immunodeficient athymic nude mouse.

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Feasibility of utilizing human tumors as first transplant generation xenografts in the normal immunocompetent mouse for determining tumor sensitivity to chemotherapeutic agents was demonstrated by applying subrenal capsule (SRC) assay methodology to fresh surgical explants in a six-day time frame. A total of 37 human breast tumors were tested in assays in which 254 xenografts were implanted into control animals. Fifty (20%) of the controls showed some degree of partial regression in the six-day assay period. Using a mean control growth having a positive change in tumor size as the criterion for evaluability, first transplant generation human breast tumors provided an evaluable assay rate of 86%. A tumor response profile was obtained as a result of testing seven clinically active drugs against 32 previously untreated breast cancers. The pattern of responses obtained indicated that no single agent was active against all tumors, nor were tumors which were responsive to one agent necessarily responsive to another, suggesting the feasibility of predicting individual tumor response to specific chemotherapeutic agents. Had these seven drugs been developmental agents of unknown activity which were being tested for the first time against such a panel of human tumors the result would have not only predicted their clinical activity, but the tumor response rates would have also provided an indication of the relative potential of each drug for the specific treatment of breast cancer.

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