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Phase I study of tandem high‐dose chemotherapy with autologous peripheral blood stem cell rescue for children with recurrent brain tumors: A pediatric blood and marrow transplant consortium study
Author(s) -
Gilman Andrew L.,
Jacobsen Chad,
Bunin Nancy,
Levine John,
Goldman Fred,
Bendel Anne,
Joyce Michael,
Anderson Peter,
Rozans Marta,
Wall Donna A.,
MacDonald Tobey J.,
Simon Steve,
Kadota Richard P.
Publication year - 2011
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22899
Subject(s) - thiotepa , medicine , carboplatin , regimen , mucositis , carmustine , surgery , chemotherapy , gastroenterology , etoposide , cyclophosphamide , cisplatin
Background High‐dose chemotherapy with autologous stem cell rescue (HDC/SCR) has produced responses and prolonged survival for some children with recurrent brain tumors, but is associated with considerable morbidity and mortality. A Phase I trial of two cycles of HDC/SCR for recurrent brain tumors in children was performed to determine the maximum tolerated doses for a novel regimen. Procedures Two cycles of HDC/SCR were given. Cycle 1 included thiotepa and carmustine given on days −5, −4, and −3. Four to six weeks later, patients received cycle 2 which included thiotepa and carboplatin given on days −5, −4, and −3. Autologous peripheral blood stem cells (PBSC) were infused on day 0 of each cycle. Results Thirty‐two patients were treated and 25 patients received both cycles of HDC/SCR. Common toxicities included mucositis, emesis, diarrhea, anorexia, and pancytopenia. Eight of 32 (25%) assessable children died from regimen‐related toxicity. Pulmonary failure occurred in seven patients. Seven patients had grade 3–4 neurotoxicity. The 3‐year event‐free survival (EFS) was 25%. Conclusions We determined the maximum tolerated regimen to be thiotepa 600 mg/m 2 and carmustine 300 mg/m 2 followed by thiotepa 600 mg/m 2 and carboplatin 1,200 mg/m 2 . Pulmonary toxicity was considerable. The toxic death rate was similar to other trials of HDC/SCR for children with recurrent brain tumors performed during the same time period. The regimen resulted in prolonged time to progression for a significant number of patients and long‐term survival for some patients with recurrent medulloblastoma and rhabdoid tumor. Pediatr Blood Cancer 2011; 57: 506–513. © 2010 Wiley‐Liss, Inc.