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Titolo:
The effect of increasing topotecan infusion from 30 minutes to 4 hours on the duration of exposure in cerebrospinal fluid
Autore:
Zamboni, WC; Luftner, DI; Egorin, MJ; Schweigert, M; Sezer, O; Richter, T; Natale, JJ; Possinger, K;
Indirizzi:
Univ Pittsburgh, Inst Canc, Program Mol Therapeut & Drug Discovery, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 scovery, Pittsburgh, PA 15213 USA Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 eut Sci, Pittsburgh, PA 15213 USA Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 l Oncol, Pittsburgh, PA 15213 USA Humboldt Univ, Univ Klinikum Charite, Med Klin & Poliklin 2, Berlin, Germany Humboldt Univ Berlin Germany te, Med Klin & Poliklin 2, Berlin, Germany Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 armacol, Pittsburgh, PA 15213 USA
Titolo Testata:
ANNALS OF ONCOLOGY
fascicolo: 1, volume: 12, anno: 2001,
pagine: 119 - 122
SICI:
0923-7534(200101)12:1<119:TEOITI>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; CHILDREN; TUMORS; PHARMACODYNAMICS; MEDULLOBLASTOMA; LEUKEMIA; PLASMA;
Keywords:
cerebrospinal fluid (CSF); pharmacokinetics; topotecan;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
18
Recensione:
Indirizzi per estratti:
Indirizzo: Zamboni, WC Univ Pittsburgh, Inst Canc, Program Mol Therapeut & Drug Discovery, 200 Lothrop St, Pittsburgh, PA 15213 USA Univ Pittsburgh 200 Lothrop St Pittsburgh PA USA 15213 213 USA
Citazione:
W.C. Zamboni et al., "The effect of increasing topotecan infusion from 30 minutes to 4 hours on the duration of exposure in cerebrospinal fluid", ANN ONCOL, 12(1), 2001, pp. 119-122

Abstract

Background: The development of metastatic disease throughout the neuroaxisfrom primary central nervous system (CNS) tumors and non-CNS tumors suggests the cerebrospinal fluid (CSF) is an important source of exposure for chemotherapeutic agents. In non-human primates, a 4-hour, as compared to a 30-minute, topotecan (TPT) infusion prolonged TPT exposure in the CSF. Patient and methods: We evaluated this approach in a 51-year-old woman with breast cancer metastatic to the CNS. TPT was administered at 1.5 mg/m(2)/day (cycle 1) and 1.0 mg/m(2)/day (cycles 2 and 3) as a 30-minute infusion on days 0-4, and as a 4-hour infusion on day 5. Cycles were repeated every 21 days. Plasma, lateral ventricular CSF, and lumbar CSF samples were obtained after 30-minute and 4-hour infusions, and assayed for TPT lactone and total by HPLC. A three-compartment model was used to calculate area under the plasma (AUC(plasma)) and lateral ventricular CSF (AUC(CSF)) concentation-time curves. TPT CSF penetration was calculated as the ratio of AUC(CSF) toAUC(plasma). Results: Mean +/- SD values for TPT total CSF penetration in lateral CSF after 30-minute and 4-hour infusions were 0.25 +/- 0.15 and 0.29 +/- 0.02, respectively. TPT total lumbar CSF concentration was 3-fold greater after a 4-hour as compared to a 30-minute infusion. For TPT lactone and TPT total, time >1 ng/ml in lateral CSF was 1.8- and 1.7-fold greater, respectively, for a 4-hour as compared to a 30-minute infusion. Conclusions: Prolonging TPT infusion from 30 minute to 4 hours increases the duration of exposure in the CSF. This study demonstrates the ability to develop treatment strategies of systemically administered chemotherapy to enhance cytotoxic exposure in the CSF.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 06:21:01