Double-conditioning regimens consisting of thiotepa, melphalan and busulfan with stem cell rescue for the treatment of pediatric solid tumors.
Bone Marrow Transplant
; 22(1): 7-12, 1998 Jul.
Article
em En
| MEDLINE
| ID: mdl-9678789
ABSTRACT
Major dose-limiting factors of high-dose thiotepa (TEPA) and melphalan are life-threatening mucositis and neurotoxicity. To administer a maximum dose of these drugs safely and to obtain a maximum anti-cancer effect, a double-conditioning regimen with a single grafting, two cycles of administration of a combination of TEPA (300-600 mg/m2) plus melphalan (70-150 mg/m2) with a 1-week interval was attempted in 20 patients with pediatric advanced or chemotherapy-resistant solid tumors (seven rhabdomyosarcoma, four hepatoblastoma, three neuroblastoma and four other malignancy). Combinations of TEPA plus melphalan/busulfan (Bu) (8-10 mg/kg) and TEPA plus Bu were given to four and two patients with brain tumors, respectively. In an additional two patients, three cycles of drug administration were performed. According to the results of the dose-escalating study, the maximum tolerable doses of TEPA and melphalan for children aged 2 years old or older were 1000 mg/m2 and 280 mg/m2, respectively. Mucositis was dose-limiting. Renal toxicity was also dose-limiting in young children (<2 years old). There were two treatment-related deaths (7%) (fungal pneumonia and renal tubular acidosis). Among 13 patients who received high-dose chemotherapy during CR, 10 are alive with no evidence of disease (15-59 months, median 35 months) and in 13 evaluable patients without CR, six are alive without regrowth of the disease (14-59 months, median 39 months). Thus, these novel conditioning regimens allowed us to increase the dose intensity to nearly the maximum for each drug and seemed to reduce adverse effects compared to previously reported regimens with these drugs. With regard to the effect on outcome, the results of this study seem to be encouraging, but a further study on a larger number of patients is required.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Neoplasias
Limite:
Adolescent
/
Adult
/
Child
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Child, preschool
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Humans
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Infant
Idioma:
En
Revista:
Bone Marrow Transplant
Assunto da revista:
TRANSPLANTE
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Japão