High-dose trimetrexate and minimal-dose leucovorin: a case for selective protection?
Clin Cancer Res
; 4(12): 2981-4, 1998 Dec.
Article
em En
| MEDLINE
| ID: mdl-9865909
ABSTRACT
Our objective was to find the minimum dose of leucovorin (LV; 5-formyltetrahydrofolate) needed to potentially provide selective protection of normal tissue in patients with tumors resistant to methotrexate (MTX) by virtue of transport during prolonged therapy with high-dose trimetrexate (TMTX). Based upon the known daily requirement for folate, that tumors are often resistant to methotrexate via a transport-based mechanism, and that large doses of trimetrexate can be given with large doses of leucovorin for the treatment of patients with Pneumocystis carinii, a protocol was designed to find the minimum LV dose required to allow the administration of large doses of TMTX. Patients were treated in 28-day cycles consisting of 14 consecutive days of oral TMTX (45 mg/m2 every 12 h), followed by 14 days of rest. The dose of concurrent LV was started at 5 mg/m2 twice daily. Cohorts of patients received successive half doses of LV so long as three consecutive patients had less than or equal to grade 3 toxicity. Ten patients received 29 courses of therapy. The most common toxicities encountered were thrombocytopenia (38%), mucositis (14%), and neutropenia (10%). At a LV dose of 2.5 mg/m2, toxicities were consistently limited to less than or equal to grade 3 and only one episode of grade 4 hematological toxicity. Although there was marked interpatient variability, the minimally effective LV dose for selective protection seems to be 2.5 mg/m2. If tumors are resistant to methotrexate because of decreased transport of drug (and also folate), then the same pharmacological principle used to develop TMTX/LV for the treatment of P. carinii may be applied to treatment of some patients with cancer.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucovorina
/
Trimetrexato
/
Neoplasias
/
Antimetabólitos Antineoplásicos
Tipo de estudo:
Guideline
Limite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Humans
/
Infant
Idioma:
En
Revista:
Clin Cancer Res
Ano de publicação:
1998
Tipo de documento:
Article