PMID- 8508417
OWN - NLM
STAT- MEDLINE
DCOM- 19930713
LR  - 20190620
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 72
IP  - 1
DP  - 1993 Jul 1
TI  - A phase II evaluation of thiotepa in pediatric central nervous system 
      malignancies.
PG  - 271-5
AB  - BACKGROUND: Both thiotepa and its active metabolite, tepa, efficiently cross the 
      blood-brain barrier. After intravenous administration, the cerebrospinal fluid 
      concentrations achieved are nearly identical to those in plasma. This provides a 
      strong rationale for testing this agent against brain tumors. METHODS: Sixty 
      pediatric patients with recurrent primary brain tumors were treated on a 
      multiinstitutional Phase II study of intravenous thiotepa at a dose of 65 mg/m2 
      administered every 3 weeks. This dose is the result of a prior pediatric Phase I 
      trial and is significantly higher than those previously recommended. RESULTS: 
      Three of 13 assessable patients with medulloblastoma had partial responses 
      lasting 22, 25, and 54 weeks. Although no objective responses were observed in 16 
      assessable patients with malignant gliomas and 14 with brain stem gliomas, 5 of 
      16 and 4 of 14 patients in these respective strata had prolonged periods of 
      stable disease (SD) lasting from 12 to more than 33 weeks. Nine assessable 
      patients with ependymoma had no objective response, but two had SD, both for more 
      than 33 weeks. Myelosuppression was the principle toxic effect encountered and 
      appeared to be more severe in patients who had received prior craniospinal 
      radiation therapy or nitrosourea therapy. CONCLUSIONS: By conventional Phase II 
      criteria, thiotepa appears to have activity in medulloblastoma. Based on several 
      patients with prolonged SD, it also may possess some limited activity in brain 
      stem and malignant gliomas. The steep in vitro dose-response curve of thiotepa 
      and the long durations of response or SD observed with the dose reported here 
      suggest that moderate-dose to high-dose thiotepa with cytokine support or 
      autologous bone marrow rescue may be associated with an improved response rate to 
      this agent.
FAU - Heideman, R L
AU  - Heideman RL
AD  - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892.
FAU - Packer, R J
AU  - Packer RJ
FAU - Reaman, G H
AU  - Reaman GH
FAU - Allen, J C
AU  - Allen JC
FAU - Lange, B
AU  - Lange B
FAU - Horowitz, M E
AU  - Horowitz ME
FAU - Steinberg, S M
AU  - Steinberg SM
FAU - Gillespie, A
AU  - Gillespie A
FAU - Kovnar, E H
AU  - Kovnar EH
FAU - Balis, F M
AU  - Balis FM
AU  - et al.
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 905Z5W3GKH (Thiotepa)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Brain Neoplasms/*drug therapy
MH  - Cerebellar Neoplasms/drug therapy
MH  - Child
MH  - Child, Preschool
MH  - Drug Administration Schedule
MH  - Ependymoma/drug therapy
MH  - Female
MH  - Glioma/drug therapy
MH  - Humans
MH  - Infant
MH  - Male
MH  - Medulloblastoma/drug therapy
MH  - Neoplasm Recurrence, Local/*drug therapy
MH  - Thiotepa/*administration & dosage/adverse effects
EDAT- 1993/07/01 00:00
MHDA- 1993/07/01 00:01
CRDT- 1993/07/01 00:00
PHST- 1993/07/01 00:00 [pubmed]
PHST- 1993/07/01 00:01 [medline]
PHST- 1993/07/01 00:00 [entrez]
AID - 10.1002/1097-0142(19930701)72:1<271::aid-cncr2820720147>3.0.co;2-k [doi]
PST - ppublish
SO  - Cancer. 1993 Jul 1;72(1):271-5. doi: 
      10.1002/1097-0142(19930701)72:1<271::aid-cncr2820720147>3.0.co;2-k.