Three tumor sensitivity tests evaluated with mouse tumors

Abstract

The predictive value of three types of tumor sensitivity tests was evaluated using mouse tumors. Sensitivities of osteosarcoma C22LR, Lewis lung and M2661 carcinoma were determined for the following drugs: DNA interacting or alkylating agent (doxorubicin, cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea, melphalan), antimetabolite (5-fluorouracil, methotrexate) and microtubule inhibitor (vinblastine, vincristine). Volume measurements of the subcutaneously growing tumors after treatment with the same drugs were considered to be the traditional reference system with which the results of the in vitro clonogenic assay, the labeled precursor incorporation assay and the subrenal capsule assay were compared. Results obtained with the in vitro clonogenic assay were highly reproducible. With the 1-h drug exposure technique the predictive accuracy was 71%. This result is in the same range as those found by others for human tumors. Predictive accuracy after continuous drug exposure was only 25%. Vinblastine, vincristine and cisplatin caused no inhibition of labeled precursor incorporation. However, the assay is too unreliable to use, due to the extreme variability when used with the other drugs. From 31 consecutively performed duplicate tests in the subrenal capsule assay, nine showed opposite results. This degree of disagreement between duplicate test results was considered too high to make reliable predictions of tumor sensitivity with this assay.