[Role of high-dose chemotherapy with hemopoietic stem-cell support in the treatment of adult patients with high-grade glioma].
Despite surgery, post-operative irradiation and adjuvant conventional chemotherapy, prognosis of high-grade gliomas remains poor. Carmustine (BCNU) has been shown to have limited activity at conventional dosage but is still the standard chemotherapy. Activity of chemotherapy is limited by the blood-brain barrier impermeability and high levels of expression of multidrug resistance proteins on tumor and/or endothelial cells. Despite high response rates, development of intra-arterial chemotherapy remains limited because of frequent acute brain toxicity related to drug administration. High-dose intravenous chemotherapy rescued by autologous hemopoietic stem cell transplantation is an alternative that might increase drug delivery through the blood-brain barrier and tumor control. Several phase I-II trials using high-dose BCNU were published. The maximum tolerated dose seems to be 800 mg/m2 and interstitial pneumonitis and hepatitis are dose-limiting toxicities. Few phase I-II trials of high-dose therapy were published using drug combinations. High response rates in patients with progressive tumor were observed and in adjuvant setting, encouraging results in terms of median survival time and long survivors were published. No phase III trial was reported to date. Future investigations should include randomized trials comparing high-dose and conventional-dose chemotherapy and development of new high-dose regimens that incorporate new drugs such as temozolomide.
Linassier
C
C
Comité multi-disciplinaire de neuro-oncologie, CHU Bretonneau, 2, boulevard Tonnellé, Tours Cedex 01.
Destrieux
C
C
Benboubker
L
L
Alcaraz
L
L
Bergemer-Fouquet
A M
AM
Jan
M
M
Calais
G
G
Colombat
P
P
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001254:Astrocytoma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005047:Etoposide / Q000008:administration & dosage; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D014182:Transplantation, Autologous
D005047:Etoposide; D002945:Cisplatin; D002330:Carmustine
Place de la chimiothérapie intensive avec autogreffe de cellules souches hématopoïétiques dans le traitement des tumeurs gliales de haut grade chez l'adulte.