HIGH-DOSE THIOTEPA AND ETOPOSIDE-BASED REGIMENS WITH AUTOLOGOUS HEMATOPOIETIC SUPPORT FOR HIGH-RISK OR RECURRENT CNS TUMORS IN CHILDREN ANDADULTS

The prognosis in patients with primary brain tumors treated with surge ry, radiotherapy and conventional chemotherapy remains poor. To improv e outcome, combination high-dose chemotherapy (HDC) has been explored in children, but rarely in adults, This study was performed to determi ne the tolerability of three-drug combination high-dose thiotepa (T) a nd etoposide (E)-based regimens in pediatric and adult patients with h igh-risk or recurrent primary brain tumors. Thirty-one patients (13 ch ildren and 18 adults) with brain tumors were treated with high-dose ch emotherapy: 19 with BCNU (B) and TE (BTE regimen), and 12 with carbopl atin (C) and TE (CTE regimen). Patients received growth factors and he matopoietic support with marrow (n = 15), peripheral blood progenitor cells (PBPC) (n = 11) or both (n = 5), The 100 day toxic mortality rat e was 3% (1/31), Grade III/IV toxicities included mucositis (58%), hep atitis (39%) and diarrhea (42%). Five patients had seizures and two ha d transient encephalopathy (23%). All patients had neutropenic fever a nd all pediatric patients required hyperalimentation, Median time to e ngraftment with absolute neutrophil count (ANC) >0.5 x 10(9)/l was 11 days (range 8-37 days). Time to ANC engraftment was significantly long er (P = 0.0001) in patients receiving marrow (median 14 days, range 10 -37) than for PBPC (median 9.5 days, range 8-10), Platelet engraftment >50 x 10(9)/l was 24 days (range 14-53 days) in children, In adults, platelet engraftment >20 x 10(9)/l was 12 days (range 9-65 days). In 1 1 patients supported with PBPC, there was a significant inverse correl ation between CD34(+) dose and days to ANC (rho = -0.87, P = 0.009) an d platelet engraftment (rho = -0.85, P = 0.005), with CD34(+) dose pre dicting time to engraftment following HDC. Overall, 30% of evaluable p atients (7/24) had a complete response (CR) (n = 3) or partial respons e (PR) (n = 4), Median time to tumor progression (TTP) was 7 months, w ith an overall median survival of 12 months. These TE-based BCNU or ca rboplatin three-drug combination HDC regimens are safe and tolerable w ith promising response rates in both children and older adults.