Treatment > Carmustine · Stem Cells

Meeting Abstract

Phase III study comparing high-dose BCNU with autologous blood stem cell support versus standard dose BCNU, in combination with radiotherapy after gross total resection in patients with supratentorial glioblastoma

C. Linassier, M. Ben Hassel, D. Figarella-Branger, J.-O. Bay, H. Bourgeois, T. Lesimple, J.-P. Cottier, L. Taillandier, R. Delepine, D. Frappaz

for the Groupe de Neuro Oncologie de la FNCLCC; CHU Bretonneau, Tours, France; Centre Eugene Marquis, Rennes, France; CHU La Timone, Marseille, France; Centre Jean Perrin, Clermont-Ferrand, France; CHU la Mileterie, Poitiers, France; Centre Alexis Vautrin, Nancy, France; Centre Leon Berard, Lyon, France.

Purpose. Based on results from a phase II trial suggesting a survival benefit of high-dose BCNU, we conducted a phase III multicenter trial to compare the efficacy of high-dose BCNU versus standard dose BCNU, in combination with radiotherapy.

Methods. Eligible criteria were age 16-65, supratentorial glioblastoma, gross total resection, performance status (PS) 0-2, adequate liver, hematological, renal, lung function, written consent.
Patients (pts) were randomized between:
intensive arm (ARM A): high-dose BCNU (800 mg/m²) followed by autologous blood stem cell rescue (day 3) and, 1 month later irradiation of the tumor bed with margins of 2 cm, 60 Gy in fractions of 1.8 Gy;
standard arm (ARM B): radiation therapy followed by chemotherapy with BCNU 80 mg/m² every 6 weeks for 1 year.
In both arms pts were followed on an outpatients basis.
Post-operative imagery and pathological slides were reviewed.

Results. 69 pts, 47 men, 22 women, median age 50.8 years were included from September 1997 to November 2001, 36 pts in arm A and 33 in arm B.
In arm B, 1 patient developed reversible grade 4 liver toxicity.
In arm A, 11 pts had grade 4 neutropenia (1 died from septic shock) and 4 had grade 4 pulmonary fibrosis (3 died from ARDS).
The study discontinuation criterion had been defined as a treatment related mortality (TRM) rate greater than 10% in arm A, so that the inclusions were stopped.
The median follow up time was 23 months.
The median overall survival (OS) was 14 months in arm A and 17.3 months in arm B (p=0.62).
The time to progression (TTP) was 6.5 months in arm A and 8.5 months in arm B (p=0.98).

Conclusion. Despite encouraging data from previous phase II trial in our group, high-dose BCNU resulted in a high TRM rate.
The survival was high in both arms, probably because of the selection of pts with good prognostic factors (age, resection, PS i.e.).
Though only 69/140 pts were included no trend in terms of OS and TTP supported a possible benefit from high-dose BCNU.

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