Chemotherapeutic regimens in present use for recurrent glioma have substantial 
toxicity. Activity against recurrent gliomas has been reported for both 
tamoxifen and interferon alpha, agents that have more acceptable toxicity 
profiles and that can be administered in an outpatient setting. We tested the 
efficacy and toxicity of the combination of high-dose tamoxifen and interferon 
alpha in adults with recurrent glioma in a phase II trial. Eligible patients had 
radiographically measurable recurrent gliomas of any grade after initial 
radiation therapy. Interferon-alpha [6 x 10(6) U subcutaneously three times per 
week] and tamoxifen (240 mg/m2/day orally) were administered continuously. 
Treatment response was assessed at 6 week intervals using clinical and 
radiographic criteria. Eighteen patients (11 males and 7 females) were enrolled. 
Median age was 41 years (range 23-61 years). All patients had gliomas that 
progressed after radiation therapy and nitrosourea chemotherapy. The histologic 
diagnosis of the original tumor was glioblastoma multiforme in 8 patients, 
anaplastic astrocytoma in 5 patients, astrocytoma in 4 patients and mixed 
malignant glioma in 1 patient. Reversible moderate to severe neurological 
toxicity manifested by dizziness and unsteady gait was seen at tamoxifen doses 
of 240 mg/m2/day. Although the initial tamoxifen dose was reduced to 120 
mg/m2/day, moderate neurotoxicity was noted at this dose as well and the trial 
was closed early. The combination of oral tamoxifen (120 to 240 mg/m2/day) and 
subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated 
with significant neurotoxicity in this group of recurrent glioma patients, 
resulting in early study closure. Of 16 evaluable patients, 12 had progressive 
disease after one cycle of treatment, 3 had stable disease, and there was one 
minor response. Gradual dose escalation may be required if similar patients are 
to be treated with high dose tamoxifen in conjunction with interferon.