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Phase III Trial of BCNU Plus Cisplatin (CDDP) Versus BCNU Alone, and Standard Radiation Therapy (SRT) Versus Accelerated Radiation Therapy (ART) in Glioblastoma (GBM) Patients: NCCTG/SWOG Results

Heather Jones, MD

University of Pennsylvania Cancer
Ultima Vez Modificado: 13 de mayo del 2001

Presenter: J.C. Buckner
Affiliation: Mayo Clinic, Rochester, MN

Background:

The adjuvant treatment for GBM is radiation therapy plus or minus BCNU. With this therapy, the median survival is about 10 months and the 5- year overall survival is about 1%. With such poor outcomes, new therapeutic approaches are needed. This study was designed to 1) To compare survival in GBM patients treated with BCNU + RT vs. BCNU CDDP given before, during and after radiation therapy (RT), and 2) to compare survival in GBM patients treated with Standard RT vs. Accelerated RT in a 2x2 factorial design.

Materials and Methods:

• Eligible patients had a supratentorial GBM with Performance Status 0-2 and no prior non- surgical therapy.
• Patients were randomly assigned to 1 of 4 treatment arms: group A = BCNU + SRI; group B = BCNU + ART; group C = BCNU + CDDP Standard RT; group D = BCNU CDDP + Accelerated RT.
• Radiation was scheduled to begin week one in groups A-B and week 8 in groups C-D.
• Standard RT = 64.8 Gy in 36 fractions/36 days. Accelerated RT = 48.0 Gy in 30 fractions/15 days.
• In groups A-B, chemotherapy = BCNU 200 mg/m2 dl q8 weeks x 6, starting with Radiation therapy on day one.
• In groups C-D, chemotherapy = BCNU 50 mg/m2/day days 1-3 every 8 weeks x 2, plus CDDP 30 mg/m2/day days l-3 and 29-31 q 8 weeks x 2, then, after radiation therapy, BCNU 200 mg/m2 day l q8 weeks x 4.

Results:

• Of 451 patients randomized, 405 (90%) were eligible for the study.
• With 351(87%) deaths, median survival (months) for the 4 randomized arms: A=10.8; B=9.4; 0=11.5; 0=11.6 (logrank p= 0.17).
• Median survival for BCNU alone (A+B) vs BCNU and CDDP(C+D) = 10.1 vs 11.6 months (stratified logrank p=0.25).
• Median survival for Standard RT (A+C) vs Accelerated RT (B+D) = 11.2 vs. 10.6 months (stratified logrank p= 0.17).
• There was greater toxicity both hematological and non-hematological (neuropathy and hearing loss) in the CDDP and BCNU group compared to the BCNU group alone.

Authors' Conclusions

BCNU + CDDP given prior to and concurrently with RI does not improve survival. Standard RT and Accelerated RT are not associated with significantly different survival, although there is a trend toward decreased survival with Accelerated RT + BCNU alone.

Clinical/Scientific Implications:

This study indicates, as in previous retrospective studies, for the treatment of GBM, more is not necessarily better. In addition, as demonstrated in retrospective studies, adding CDDP to BCNU does not add to survival but does cause increased toxicity. Accelerated RT does not improve OS. We do look forward to the follow up data on neurological function in this group. This will give us insight into the question of safely reducing overall treatment time.