Sensitivity of short-term cultures derived from human malignant glioma to the anti-cancer drug temozolomide

The activity of temozolomide, which has shown clinical activity against malignant glioma, has been assessed in vitro against short-term cultures derived from these tumors using an intermediate duration microtitration assay with MTT reduction as the end-point. This assay has previously been shown to correlate closely with a monolayer clonogenic assay. Sensitivity was assessed in 15 short-term cultures (passage levels 3-9) derived from WHO grade III and IV astrocytomas. These cultures had a median ID(50) value of 258 mu M for temozolomide and 16.13 mu M for CCNU. Maximum serum concentrations of temozolomide are of the order of 75 mu M but only three of 15 (20%) cultures had ID(50)s below this value. Fourteen of 15 (93%) cultures displayed cross-resistance between temozolomide and CCNU, although one line which was extremely resistant to CCNU retained sensitivity to temozolomide. Comparative studies of published clonogenic survival curves indicate that the shortterm glioma cell lines used in this study have similar sensitivities to established glioma cell lines, whilst colon carcinoma cell lines and bladder carcinoma are often more resistant to these drugs. Cell lines from testicular teratoma cell lines may show exquisite sensitivity to temozolomide and this level of sensitivity is seen only occasionally in shortterm cultures derived from malignant glioma, [(C) 1999 Lippincott Williams & Wilkins.].