[High dose chemotherapy with thiotepa, carboplatin, VP16 and autologous stem cell transplantation in treatment of malignant brain tumors with poor prognosis. Results of a mono-center pilot study].
More than half of the children and adolescents with malignant brain tumors will relapse following initial therapy. Irrespective of the therapeutic modalities the prognosis of patients with recurrent or metastatic brain tumors is still poor. New strategies such as high dose chemotherapy (HDCT) with autologous blood stem cell transplantation (ABSCT) offer the possibility to improve the longterm prognosis of these patients. Following conventional chemotherapy with carboplatin/etoposide and after achieving complete or partial remission (CR or PR) 10 patients aged from 3.2 to 25.5 years (median, 10.3 years) with refractory or recurrent malignant brain tumors (anaplastic astrocytoma/glioblastoma, n = 2; medulloblastoma/PNET, n = 6; ependymoma, n = 1; plexus carcinoma, n = 1) received in a pilot study one course of HDCT with ABSCT. The consolidation regimen consisted of thiotepa (400-600mg/m2/d, i.v. 6 h, d-9), carboplatin and etoposide (500mg/m2/d, CVI 24h, d-8 to d-5, respectively) and was followed by the retransfusion of autologous blood stem cells on day 0. Before starting HDCT 6 patients showed CR and 4 patients had PR or stable disease (SD). Following the HDCT 3 of the 4 patients with residual tumor had CR or PR. 6 patients have remained in continuous CR or SD 8 to 41 months (median 17.2 months) after the HDCT. 2 patients relapsed 8.5 and 9.5 months after HDCT and died from progressive disease. Two patients died therapy-related from systemic aspergillosis and were not evaluable for response. Hematological recovery with an absolute neutrophile count of > 0.5 x 10(9)/l and a platelet count of > 30 x 10(9)/l was reached on days +11 (median; range, +9 to +14) and +16 (median; range, +6 to +47), respectively. The main nonhematological toxic effects were infections, severe mucositis, and hyperbilirubinemia. Although the long-term efficacy of HDCT with ABSCT is still not evaluable and the toxicity of this regimen is high, a multicenter phase II trial seems to be justified in view of the poor prognosis of recurrent or refractory brain tumors in children and adolescents.
Fleischhack
G
G
Abt. Päd. Hämatologie/Onkologie, Universitätskinderklinik Bonn.
Pöpping
K
K
Hasan
C
C
Utsch
B
B
Jüttner
J
J
Bode
U
U
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D010865:Pilot Projects; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects
D005047:Etoposide; D013852:Thiotepa; D016190:Carboplatin