Response of cultured human brain tumors to nitrosoureas: correlation with clinical data

An in vitro microcytotoxicity assay was utilized to determine the sensitivity of 58 cultured human malignant gliomas to the chemotherapy agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Of 58 such tumors, 42 (72%) showed a statistically significant cytotoxic response to BCNU in this assay. For those responding tumor lines, the cytotoxic index ranged from 0.25 to 0.76, with most clustered at the 0.40 level. To determine the therapeutic predictive relevance of such microcytotoxicity testing, the clinical course of patients receiving postoperative radiation therapy plus two or more doses of nitrosourea chemotherapy, as well as two or more computerized tomographic scans, was evaluated. In the 14 patients meeting all these criteria, tumor size increased in all five patients whose tumors did not respond to BCNU in the microcytotoxicity test. Six of the nine patients whose tumors in culture showed significant sensitivity to BCNU in vitro showed a clear decrease in tumor size over periods ranging from 17 to 48 months. Tumors in two patients increased in size, and one remained unchanged over the interval studied. These data support the concept that in vitro microcytotoxicity testing can be predictive of clinical response. Further study of this correlation seems warranted.