Procarbazine and high-dose tamoxifen as a second-line regimen in recurrenthigh-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 (PC B) 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 i n 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 w ith a first-line nitrosourea-based chemotherapy regimen (group A), and 19 p atients had also been pretreated with a second-line chemotherapy regimen co nsisting of carboplatin and teniposide (group B). Twenty-one of the patient s 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 glioblast oma 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 in terval [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 reas onably high response rate in patients with heavily pretreated high-grade gl iomas. However, although it resulted in an improvement in the patients' qua lity of life and/or performance status, it war not followed by an increased TTP or MST. (C) 1999 by American Society of Clinical Oncology.