Salvage Chemotherapy With Tamoxifen for Recurrent Anaplastic Astrocytomas

Abstract

BACKGROUND: A prospective phase 2 study of daily oral tamoxifen citrate in young adults with recurrent anaplastic astrocytomas. METHODS: Twenty-four patients (15 men; 9 women) aged 19 to 45 years (median age, 31.5 years) with recurrent anaplastic astrocytomas were treated. All patients had been treated previously with surgery and involved-field radiotherapy (median dose, 60 Gy; range, 59-61 Gy). In addition, 22 patients were treated adjuvantly with nitrosourea-based chemotherapy (combined procarbazine hydrochloride, lomustine, and vincristine sulfate in 16; carmustine in 6). All patients were treated with salvage chemotherapy at first recurrence, with 1 to 4 chemotherapy regimens (median, 1 regimen). Tamoxifen citrate was administered orally at a fixed dosage of 80 mg/m2 as a single or a twice-daily dosage. Neurologic and neuroradiographic evaluation were performed every 12 weeks, operationally defined as a single cycle of tamoxifen. RESULTS: All patients were able to undergo evaluation. A median of 4 cycles of tamoxifen (range, 1-8 cycles) were administered. No tamoxifen-related toxic effects were seen, nor were there any treatment-related deaths. Four patients (17%) demonstrated a neuroradiographic partial response; 11 patients (46%), stable disease; and 9 patients (38%), progressive disease following a single cycle of tamoxifen. Time to tumor progression ranged from 3 to 25 months (median, 12 months). Survival ranged from 3 to 27 months (median, 13 months). Five patients are alive, with 3 receiving alternative chemotherapy regimens and 2 continuing to receive tamoxifen. In the group with responding and stable disease, median survival was 15 months (range, 8-27 months). CONCLUSION: Tamoxifen demonstrated modest efficacy with no apparent toxic effects in this heavily pretreated cohort of young adults with recurrent anaplastic astrocytomas.