Phase I/II Trial of Dose-Escalated Busulfan Delivered by Prolonged Continuous Infusion in Allogeneic Transplant Patients.
Biol Blood Marrow Transplant
; 21(12): 2129-2135, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26210442
ABSTRACT
Intensive chemotherapy or chemotherapy plus irradiation and allogeneic stem cell transplantation can be curative for patients with hematologic diseases. Reduced-intensity transplants can also achieve cure and result in less treatment-related mortality but higher relapse rates. Thus, optimizing the conditioning regimens used in allogeneic transplantation remains an important goal. We conducted a phase I/II trial to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a continuous infusion of busulfan over 90 hours in conjunction with fludarabine followed by allogeneic related or unrelated donor transplant. Fifty-four patients with advanced hematologic malignancies were enrolled on this study. The MTD was identified as a 24-hour area under the curve (AUC) of approximately 7095 µM/min, which represents a 43% increase over the standard total daily AUC dose of 4800 µM/min given by intermittent schedules. DLTs at doses over 8000 µM/min were identified by a desquamative skin rash and mucositis. No dose-related increase in hepatic, pulmonary, or other organ toxicities were seen, whereas efficacy appeared to be improved at higher dose levels. Continuous-infusion busulfan with intermittent fludarabine provides an alternative treatment strategy that is generally well tolerated and permits an increase in total busulfan dose with encouraging efficacy. (NCI study no. NCT00448357.).
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vidarabina
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Bussulfano
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Transplante de Células-Tronco Hematopoéticas
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Neoplasias Hematológicas
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Condicionamento Pré-Transplante
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Agonistas Mieloablativos
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Biol Blood Marrow Transplant
Assunto da revista:
HEMATOLOGIA
/
TRANSPLANTE
Ano de publicação:
2015
Tipo de documento:
Article