Elmustine

For the non-operable malignant glioma patients, prognosis remains poor, with a survival of 8 months for the glioblastomas (G), and 15 months for anaplastic astrocytomas (AA). 27 histologic proven malignant gliomas (17 AA and 10 G) were treated between April 1991 and June 1992. Median age was 48 years. The therapeutic protocol consisted of three courses of intra arterial chemotherapy (IAC) with ACNU, at intervals of six weeks, and a localised 60 Gy radiotherapy between the first and the second IAC course. 72 courses of IAC were delivered (2.4 per patient). Response rate was 51.8%. Median survival (MS) was 13 months, with a survival rate of 28% at 24 months. For the AA, MS was 21 months, with a survival rate of 37% at 24 months. For the G, median survival was 10 months. Responders were 65% for AA, 30% for G. Non responders all died before 24 months had relapsed with a MS of 9 months. 54% of responding patients had a 2 years survival. Toxicity were acceptable with 7% of haematological toxicity and partial loss of visual acuity in 11% of the case. No chronic neurological sequellae were noted. We compare theses results with two previous trials, concerning inoperable patients, treated by association of radiotherapy and systemic chemotherapy. Survival seems to be equivalent with HeCNU and with this treatment, but toxicity decrease with ACNU. Early radiotherapy does not increase complications. This treatment can be used for patients with inoperable malignant gliomas.

In the present study a slightly modified MTT assay was used in conjunction with cell counting to determine the antiproliferative efficacy of N-(2-chloroethyl)-N-nitroso-N'-2-hydroxyethylurea (HECNU), vinblastine, and hexadecylphosphocholine (HPC) in a panel of six tumor cell lines. This panel consisted of two human (MDA-MB231, MCF-7) and two rodents (1/C2, 1/C32) mammary-carcinoma cell lines as well as of two tumor cell lines of gastrointestinal origin (HT-29, KB). It was shown that the use of acid isopropanol as a solvent of the formazan crystals produced correlations between cell number and absorption that were as good as, if not better than, those seen after dimethylsulfoxide (DMSO) application. The optimal period of incubation with the MTT dye was 2 h. A comparison of the antiproliferative activity of HECNU revealed that the HT-29 cell line was most resistant [50% inhibition concentration (IC50), 138.7 mumol/l], followed by MCF-7 cells (IC50, 127.7 mumol/l), whereas MDA-MB231 cells showed the highest sensitivity (IC50, 6 mumol/l). Vinblastine induced the highest (MCF-7 cells; IC50, 0.68 nmol/l) and the lowest (1/C2 cells; IC50, 7.69 nmol/l) degrees of growth inhibition in cell lines derived from mammary carcinoma. This contrasted with the activity of HPC, which was considerably less effective in the four mammary-carcinoma cell lines (IC50 from 29.4 to 69.9 mumol/l) than in the two cell lines of gastrointestinal origin (IC50, 1.9 and 3.1 mumol/l). Interestingly, treatment with HPC stimulated the growth of 1/C32 cells in the lower dose range. After treatment with HECNU, the average IC50 value determined in the MTT assay was 2.4-fold that disclosed by cell counting, whereas the average values found for HPC and vinblastine by both methods corresponded fairly well, with the respective values obtained using the MTT assay being only 26% and 14% higher than those measured by cell counting. A dose-dependent increase in the mean size of MCF-7 cells was observed after exposure to HECNU, which--if taken into account--considerably reduced underestimation of this parameter by the MTT assay. No variation in cell size was noted following treatment with HPC and vinblastine. Thus, depending on the antitumor agent used, the MTT assay can result in slight or even considerable underestimation of the antitumor efficacy of certain compounds and may need correction by consideration of the effect of the drugs on cell size.