Radiotherapy combined with nimustine hydrochloride and etoposide for malignant gliomas: results of a pilot study

The aim of this study was to examine the effectiveness of radio-chemotherapy using nimustine hydrochloride (ACNU) and etoposide (VP-16) for malignant gliomas.

From 1985 through 1998, 33 consecutive patients with supratentorial malignant gliomas were treated by a single protocol. The mean age was 45.8 years (range 12-76 years). The median Karnofsky performance score was 80 (range 60-100). There were 14 anaplastic astrocytomas (AA) and 19 glioblastomas (GBM). Following surgery, 60 Gy of radiotherapy combined with an adjuvant chemotherapy using ACNU (80 mg/m(2) i.v. days 1 and 36) and etoposide (80 mg/m(2) i.v. days 2, 3, 37 and 38) was administered. On completion of the initial radio-chemotherapy, a single cycle of the same chemotherapy was repeated every 6-8 weeks until tumor progression or for 2 years at the maximum.

All 33 patients tolerated treatment. We observed complete response in five cases (15%), partial response in nine (27%), no change in 11 (33%) and progressive disease in eight (24%). The response rate (>50% reduction) was therefore 42.4%. Median progression-free survival (PFS) for all 33 patients was 8.4 months: 7.8 months for GBMs and 13.5 months for AAs. There was no significant difference in PFS between GBM and AA patients (p = 0.14). The median survival time of all 33 patients was 21.1 months: 16.2 months for GBMs and 49.9 months for AAs. The difference in survival between AA and GBM was statistically significant (p = 0.0019). Myelosuppression appeared in 11 patients: grade 2 hematological toxicity in 10 cases (30%) and grade 3 in one case (3%). We did not observe any gastrointestinal toxicity. Multivariate analysis showed that age and initial histological grade had independent prognostic significance.

RT with ACNU and etoposide are feasible and well tolerated and the treatment results were comparable to the best results reported in the literature.