Etoposide with or without mannitol for the treatment of recurrent or primarily unresponsive brain tumors: a Children's Cancer Group Study, CCG-9881.
OBJECTIVE
This study was undertaken to evaluate the response of recurrent brain tumors to intravenous etoposide and to evaluate the efficacy of mannitol in augmenting etoposide's tumoricidal effect.


METHODS
Ninety-nine children between one and 21 years of age with recurrent brain tumors were randomly assigned to treatment with intravenous etoposide 150 mg/M2, with or without mannitol 15 gm/M2, daily for five days every three weeks for one year or until disease progression or death. Computerized tomographic (CT) or magnetic resonance image (MRI) scans, obtained after three cycles of therapy, were compared with pre-therapy scans. Scans were centrally reviewed.


RESULTS
Of 87 evaluable patients, 12 (13.8%) were determined to have had an objective response by the institutional radiologist. On central review, 7/66 (10.6%) responses were documented. Responses in centrally reviewed patients were observed in 2/12 (16.7%) low grade astrocytomas, 4/26 (15.4%) medulloblastoma or primitive neuroectodermal tumors (PNET), 1/13 (7.7%) high grade astrocytomas and 0/15 (0%) brain stem gliomas. Survival at one year was 53% (SE 12%) for low grade astrocytomas, 38% (SE 7%) for medulloblastoma or PNET, 28% (SE 10%) for high grade astrocytomas and 9% (SE 5%) for brain stem gliomas. An effect of mannitol was not observed.


CONCLUSIONS
Intravenous etoposide has a low level of activity in the treatment of recurrent low grade astrocytomas and medulloblastoma or PNET. The efficacy of this agent was not enhanced by the coincident intravenous administration of mannitol.
Kobrinsky
N L
NL
Roger Maris Cancer Center, Fargo, ND, USA.
Packer
R J
RJ
Boyett
J M
JM
Stanley
P
P
Shiminski-Maher
T
T
Allen
J C
JC
Garvin
J H
JH
Stewart
D J
DJ
Finlay
J L
JL
D000293:Adolescent; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008353:Mannitol / Q000009:adverse effects / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016019:Survival Analysis; D017211:Treatment Failure
D000972:Antineoplastic Agents, Phytogenic; D008353:Mannitol; D005047:Etoposide