ABSTRACT
BACKGROUND: Patients with malignant astrocytomas (MA) have a poor survival rate despite surgery, radiation therapy (RT), and chemotherapy (CT). Patients deteriorate rapidly with decreasing quality of life (QoL). The purpose of the current study was to determine the safety and efficacy, including QoL evaluation, of oral therapy with temozolomide, thalidomide, and tamoxifen (TTT) in patients with MA in an Institutional Review Board (IRB)-approved, prospective trial. PATIENTS AND METHODS: Twenty-three patients met the eligibility requirements and were enrolled after informed consent was signed. After baseline testing, patients received temozolomide 75 mg/m2 orally (p.o.) for the first 21 days, thalidomide 100 mg p.o. daily, and tamoxifen 100 mg p.o. daily for each 28-day cycle. Treatment continued until disease progression. Primary outcome measurements were survival (Kaplan-Meier analysis), response to treatment, toxicity (National Cancer Institute's Common Toxicity Criterion) and QoL evaluation. RESULTS: The Kaplan-Meier analysis showed that survival time from diagnosis was 78.4+/-15 weeks with a median survival of 54.6 weeks and from date of enrollment was 46.1+/-10 weeks with median survival of 33.3 weeks. Toxicity was limited to 5 patients with deep venous thrombosis (DVT), 2 of whom had pulmonary emboli (PE). All recovered with anticoagulation therapy and none suffered long term sequelae. Several QoL measures, including the global health status scores (p=0.003), were significantly improved after 2 cycles of treatment compared to the baseline assessment. CONCLUSION: The combination of temozolomide, thalidomide and tamoxifen administered as outpatient oral therapy resulted in significantly improved QoL for patients with MA without significant toxicity.
