ATTEMPTED DOSE INTENSIFIED CYCLOPHOSPHAMIDE, ETOPOSIDE, AND GRANULOCYTE-COLONY-STIMULATING FACTOR FOR TREATMENT OF MALIGNANT ASTROCYTOMA

Patients with malignant astrocytoma continue to respond poorly to chem otherapy and have a dismal prognosis. Cyclophosphamide (CTX) and etopo side demonstrate activity against malignant astrocytoma at standard do sages, with bone marrow suppression as the limiting toxicity. In order to allow dose intensification, minimize leukopenia, and improve effic acy granulocyte colony-stimulating factor (G-CSF) was used in combinat ion with CTX and etoposide. The protocol consisted of CTX (2 mg/m(2)/d , days 1, 2), etoposide (200-300 mg/m(2)/d, days 1-3), and G-CSF (5-10 mu g/d subcutaneously, days 4-18), every 4 weeks. Nine evaluable pati ents (7 glioblastoma multiforme, 2 anaplastic astrocytoma) were treate d, ranging in age from 26-67 (mean 41). One of 9 patients responded (1 1%) with a partial response (13+ months), 3 had stable disease (33%; 8 , 5, 2.5 months), and 5 had progressive disease (3, 2.5, 2, 1.5, 1 mon ths). The median time to progression for responders was 6.5 months, wh ile overall it was 2.5 months. Overall median survival was only 7.0 mo nths. Toxicity was frequent and severe, typically delaying treatment c ycles. The most common complications were severe myeolosuppression (9) , sepsis (8), rash (6), urinary infection (5), and anorexia (5). Treat ment delays caused by infections and other complications occurred ofte n, abrogating the intended dose intensification. The received dose int ensity (DI) for CTX was 400-425 mg/m(2)/week (relative DI0.41), while for etoposide it was 75 mg/m(2)/week (relative DI0.42). In summary, as used in this protocol, dose intensive chemotherapy with CTX, etoposid e, and G-CSF does not improve efficacy over standard regimens and resu lts in excessive toxicity.