EARLY CHEMOTHERAPY AND CONCURRENT RADIOCHEMOTHERAPY IN HIGH-GRADE GLIOMA

Purpose: The poor results from treatment of high grade glioma prompted us to explore new protocols involving concurrent radio-chemotherapy. Our primary objective was to evaluate the feasibility of very early po stoperative chemotherapy with BCNU, concurrent radio-chemotherapy with carboplatin and teniposide, and post-radiotherapy BCNU. Our secondary objectives were to evaluate time to progression, and overall survival . Patients and methods: We treated 24 newly diagnosed patients (pts) w ith BCNU 150 mg/m(2) seven days after surgery. Thirty days later, we s tarted radiotherapy, 1.8 to 2 Gy/day for 5 days a week on limited fiel ds up to 60 Gy, and concurrent chemotherapy with carboplatin 250 mg/m( 2) on days 1, 22, and 43, and teniposide 50 mg/m(2) on days 1, 2, 3, 2 2, 23, 24, 43, 44 and 45. Two cycles of 150 mg/m(2) BCNU were then giv en at 30 and 70 days, respectively, after the end of the radio-chemoth erapy course. Therapy was then suspended, but if disease progression w as evident, treatment was resumed with drugs that had not been previou sly employed. Surgical reintervention was not routinely considered. Re sults: Following radio-chemotherapy treatment in the 24 pts evaluable for response, we observed partial remissions in 8 cases (33%) and stab le disease in 12 (50%). Actuarial estimates of progression free surviv al (PFS) were 33 weeks, with 56 wks for anaplastic astrocytoma and 31 weeks for glioblastoma. Median survival time (MST) of all pts was 58 w eeks; 51 weeks for glioblastoma and was not reached for anaplastic ast rocytoma. This regimen was feasible. Of 144 planned cycles, 139 were d elivered, and among these only in 13 and 9 cycles the doses were reduc ed by 75 and 50%, respectively. We did not observe any gastrointestina l toxicity. Grade 2 hematological toxicity occurred in 25% of pts, gra de 3 in 4% and neurological toxicity in 3% of the pts during BCNU deli very, probably due to a sharp increase in intracranial pressure. Concl usion: Early chemotherapy, concurrent chemo-radiotherapy and brief pos t-radio-therapy chemotherapy are feasible and well tolerated. The obje ctive response and disease stabilization rates appear similar to previ ous experiences.