High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors.
Forty-two patients (29 newly diagnosed) with high grade gliomas (n = 37), medulloblastoma (n = 2) or non-biopsied tumors (n = 3) with supratentorial (n = 24), brain stem (n = 11), posterior fossa (n = 5) or spinal (n = 2) location were eligible for this study with adequate organ function and no bone marrow tumor infiltration. Median patient age was 12.2 years (range, 0.7-46.8). A total of 600 mg/m2 BCNU, 900 mg/m2 thiotepa and 1500 or 750 mg/m2 etoposide (VP-16) was administered followed by autologous bone marrow reinfusion (ABMR). Twenty-one newly diagnosed patients received local irradiation (RT) post ABMR. Nine early deaths were observed (21%), as well as one secondary graft failure. Half of the patients aged 18 years or older experienced toxic deaths, whereas only 15% of patients younger than 18 years experienced toxic death (P = 0.05). Of 25 evaluable newly diagnosed patients, 20% achieved complete remission (CR) and 4% partial remission (PR), while 28% remained in continuing complete remission (CCR) and 44% remained with stable disease prior to RT. Of eight evaluable patients with recurrent disease, one achieved CR and two PR, while one remained in CCR and four with stable disease for 1 to 110.2 months. Overall survival was 36%, 24% and 17% at 1, 2 and 3 years following ABMR, with three newly diagnosed patients and one patient treated for recurrent disease being alive, without disease progression 64.4, 67.0, 86.3 and 110.2 months after ABMR, respectively. The combination of high-dose BCNU/ thiotepa/VP-16 has substantial toxicity but definite activity for high risk CNS tumors. Similar protocols with lower toxicity merit further evaluation in both newly diagnosed and recurrent CNS tumors.
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
V
V
Papadakis
I J
IJ
Dunkel
L D
LD
Cramer
E
E
Kramer
E
E
Papadopoulos
S
S
Goldman
R J
RJ
Packer
M
M
Willoughby
D
D
Baker
J
J
Garvin
S
S
Strandjord
P
P
Coccia
A M
AM
Kaplan
M
M
Klemperer
J L
JL
Finlay
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity*; D016026:Bone Marrow Transplantation; D002330:Carmustine / Q000008:administration & dosage / Q000633:toxicity; D016543:Central Nervous System Neoplasms / Q000150:complications* / Q000401:mortality / Q000628:therapy*; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006085:Graft Survival; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000139:chemically induced; D008171:Lung Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000139:chemically induced; D009422:Nervous System Diseases / Q000139:chemically induced; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage / Q000633:toxicity; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D005047:Etoposide; D013852:Thiotepa; D002330:Carmustine