Procarbazine and high-dose tamoxifen as a second-line regimen in recurrent high-grade gliomas:: A phase II study

Purpose: A phase II study was conducted in patients with high-grade gliomas that recurred after surgery plus radiotherapy and a first-line nitrosourea-based regimen, Our aim was to investigate the efficacy of procarbazine (PCB) combined with high-dose tamoxifen in relation to tumor control, toxicity, and time to progression (TTP). Patients and Methods: Fifty-three patients were treated with procarbazine in repeated 30-day courses at 100 mg/m(2)/d plus tamoxifen 100 mg/d, with a 30-day interval between courses. Thirty-four patients had been pretreated with a first-line nitrosourea-based chemotherapy regimen (group A), and 19 patients had also been pretreated with a second-line chemotherapy regimen consisting of carboplatin and teniposide (group B). Twenty-one of the patients had also been procarbazine pretreated, whereas the remaining 32 patients were not procarbazine pretreated, Results: The response was assessed in 51 patients, 28 of whom had glioblastoma multiforme (GBM) and 23 of whom had anaplastic astrocytoma (AA), There were two complete responses (CR) (4%) and 13 partial responses (PR) (25.5%), The overall response rate (CR + PR) was 29.5% (SE, 6.4; 95% confidence interval [CI], 23 to 35.8), Seventeen patients (32%) had stable disease (SE, 6.2; 95% CI, 21 to 33.6), The median TTP was 13 weeks for patients with GEM and 33 weeks for patients with AA (P =.006). The median survival time (MST) was 27 weeks for patients with GEM and 57 weeks for those with AA(P =.006). Conclusion: Combined PCB and tamoxifen as a second-line regimen gave a reasonably high response rate in patients with heavily pretreated high-grade gliomas. However, although it resulted in an improvement in the patients' quality of life and/or performance status, it war not followed by an increased TTP or MST. (C) 1999 by American Society of Clinical Oncology.