title: High-dose thiotepa and etoposide-based regimens with autologous hematopoietic support for high-risk or recurrent CNS tumors in children and adults.
abstract: The prognosis in patients with primary brain tumors treated with surgery, radiotherapy and conventional chemotherapy remains poor. To improve outcome, combination high-dose chemotherapy (HDC) has been explored in children, but rarely in adults. This study was performed to determine the tolerability of three-drug combination high-dose thiotepa (T) and etoposide (E)-based regimens in pediatric and adult patients with high-risk or recurrent primary brain tumors. Thirty-one patients (13 children and 18 adults) with brain tumors were treated with high-dose chemotherapy: 19 with BCNU (B) and TE (BTE regimen), and 12 with carboplatin (C) and TE (CTE regimen). Patients received growth factors and hematopoietic support with marrow (n = 15), peripheral blood progenitor cells (PBPC) (n = 11) or both (n = 5). The 100 day toxic mortality rate was 3% (1/31). Grade III/IV toxicities included mucositis (58%), hepatitis (39%) and diarrhea (42%). Five patients had seizures and two had transient encephalopathy (23%). All patients had neutropenic fever and all pediatric patients required hyperalimentation. Median time to engraftment with absolute neutrophil count (ANC) >0.5 x 10(9)/l was 11 days (range 8-37 days). Time to ANC engraftment was significantly longer (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 11 patients supported with PBPC, there was a significant inverse correlation between CD34+ dose and days to ANC (rho = -0.87, P = 0.009) and platelet engraftment (rho = -0.85, P = 0.005), with CD34+ dose predicting time to engraftment following HDC. Overall, 30% of evaluable patients (7/24) had a complete response (CR) (n = 3) or partial response (PR) (n = 4). Median time to tumor progression (TTP) was 7 months, with an overall median survival of 12 months. These TE-based BCNU or carboplatin three-drug combination HDC regimens are safe and tolerable with promising response rates in both children and older adults.
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Papadopoulos
authors.forename: J H
authors.initials: JH
authors.lastname: Garvin
authors.forename: M
authors.initials: M
authors.lastname: Fetell
authors.forename: L T
authors.initials: LT
authors.lastname: Vahdat
authors.forename: T J
authors.initials: TJ
authors.lastname: Garrett
authors.forename: D G
authors.initials: DG
authors.lastname: Savage
authors.forename: C
authors.initials: C
authors.lastname: Balmaceda
authors.forename: J
authors.initials: J
authors.lastname: Bruce
authors.forename: M
authors.initials: M
authors.lastname: Sisti
authors.forename: S
authors.initials: S
authors.lastname: Isaacson
authors.forename: R
authors.initials: R
authors.lastname: De LaPaz
authors.forename: R
authors.initials: R
authors.lastname: Hawks
authors.forename: E
authors.initials: E
authors.lastname: Bagiella
authors.forename: K H
authors.initials: KH
authors.lastname: Antman
authors.forename: C S
authors.initials: CS
authors.lastname: Hesdorffer
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013852:Thiotepa / Q000008:administration & dosage*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D013852:Thiotepa