Radiotherapy Combined with Nimustine Hydrochloride and Etoposide for Malignant Gliomas: Results of a Pilot Study

BACKGROUND: The aim of this study was to examine the effectiveness of radio-chemotherapy using nimustine hydrochloride (ACNU) and etoposide (VP-16) for malignant gliomas. METHODS: 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. RESULTS: 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. CONCLUSION: RT with ACNU and etoposide are feasible and well tolerated and the treatment results were comparable to the best results reported in the literature.