Brain Tumors

Most patients with malignant brain gliomas relapse after surgery and RT, and die within 2 years of diagnosis. The addition of chemotherapy offers a modest survival advantage, especially for younger patients with anaplastic astrocytoma (AA), but virtually none to those with high-grade glioblastoma multiforme (GM). Standard salvage therapy is not curative. The poor outcome of adult patients with malignant gliomas prompted many trials in the 1980s of high-dose singleagent BCNU, a drug with good central nervous system (CNS) penetration.55-57 Initial trials in patients with refractory tumors showed high response rates, although of brief duration. High-dose BCNU was subsequently moved up to first-line therapy, combined with surgery and RT. Johnson et al. reported their experience in 25 patients with unresectable grade III or IV gliomas. These patients were treated with BCNU 1050 mg/m2 followed by autologous stem cell transplant and cranial radiotherapy. They reported a median survival of 26 months, significantly better than a group of historical controls albeit with short follow-up.58 The largest series was reported by

Durando et al.59 in 114 newly diagnosed patients, who were treated with surgery, high-dose BCNU, and RT. At a median follow-up of more than 7 years, the EFS and OS rates were 14 and 24%, respectively. Extent of prior surgery, histology (median OS of 12 months for GM vs 81 months for AA), and young age were predictive of outcome. These observations are consistent with those from nonconcurrent matched-pair comparisons, which did not suggest benefit from high-dose BCNU in patients with high-grade GM.60

In summary, available results of HDC in adult patients with high-grade GM, largely employing highdose single-agent BCNU, do not appear to improve outcome compared to conventional therapy. Further research may identify a role of HDC, in the setting of multimodal treatment, for young patients with AA.

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