Brain and Spinal Cord cancer treatment summaries: Glioblastoma multiforme (temodar- XRT)

The natural history of glioblastoma multiforme, the most common of all brain tumors were discussed in detail. The median survival of all GBM patients has traditionally been reported as 12 months. The most important  prognostic factors were  age, Karnofsky  Performance Status (KPS), extent of surgical resection, and neurologic function.

For the past two decades there has been a paucity of large randomized clinical trials focusing on GBM. At ASCO 2004, one of the plenary sessions was presented by by Roger Stupp et al which showed promising survival for combination of low dose temodar at 75 mg/m2 during XRT followed by full dose temodar for 6 cycles. This was a large multi-institutional trial from 85 centers which included 573 patients. Patients with GBM were randomized to either XRT alone to 60 Gy vs combination chemo/XRT. There was minimal grade 3 or 4 toxicity (7%). Progression-free survival for RT alone was 5 months and 7.2 months for RT/TMZ, p< .0001. The median survival was 12 months vs 15 months favoring RT/TMZ patients, p<.0001. Given the encouraging data, this treatment approach should be considered for all GBM patients not embarking on a clinical trial.

References:

• Shaw EG et al. Reexamining the RTOG recursive partitioning analysis for GBM patients. Int J Radiat Oncol Biolog Phys 57:s135-136, 2003.
• R Stupp et al. Concomitant and adjuvant temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme. Conclusive results of a randomized phase III trial by the EORTC Brain and RT Groups and NCIC clinical Trials Group. PASCO #2, 2004

The most significant prognostic factor in GBM is age, followed by KPS, histology and mental status. Older patients with a limited functional status do particularly badly and have median survivals of only a few months and there are no long-term survivors. Current treatment for patients with GBM including surgery, radiation therapy, and chemotherapy is partially effective but rarely cures patients of their disease. The impact of 6 weeks of XRT is particularly taxing to both patient as well as family care givers. Options for elderly include no therapy, shortened course of XRT or temozolomide monotherapy. A recent article published in the JCO by Roa et al (vol 22 May 1, 2004) examined the outcome of a shortened course of XRT (40 Gy in 15 Fx over 3 weeks vs 60 Gy in 30 fx over 6 weeks). This was a prospective randomized trial of 100 patients age 60 or greater. Overall survival times were similar in both arms (5.1 months for standard RT and 5.6 months for shortened course, log-rank test p=.57). Shorter course allowed less corticosteroid dependence and reduced treatment time.

References:

• Roa et al Abbreviated course  of radiation therapy in older patients with glioblastoma multiforme: A prospective randomized clinical trial. J Clin Oncol 22: 1583 -1588, 2004.
• Frauger et al. Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme patients in an elderly population PASCO # 308, 2002.