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Titolo:
POTENT THERAPEUTIC ACTIVITY OF IRINOTECAN (CPT-11) AND ITS SCHEDULE DEPENDENCY IN MEDULLOBLASTOMA XENOGRAFTS IN NUDE-MICE
Autore:
VASSAL G; BOLAND I; SANTOS A; BISSERY MC; TERRIERLACOMBE MJ; MORIZET J; SAINTEROSE C; LELLOUCHTUBIANA A; KALIFA C; GOUYETTE A;
Indirizzi:
INST GUSTAVE ROUSSY,LAB PHARMACOTOXICOL & PHARMACOGENET,CNRS,URA147,RUE CAMILLE DESMOULINS F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT PEDIAT F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT ANATOMOPATHOL F-94805 VILLEJUIF FRANCE RHONE POULENC RORER SA VITRY SUR SEINE FRANCE HOP NECKER ENFANTS MALAD,DEPT PEDIAT NEUROSURG PARIS FRANCE HOP NECKER ENFANTS MALAD,NEUROPATHOL LAB PARIS FRANCE
Titolo Testata:
International journal of cancer
fascicolo: 1, volume: 73, anno: 1997,
pagine: 156 - 163
SICI:
0020-7136(1997)73:1<156:PTAOI(>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
TOPOISOMERASE-I INHIBITOR; HUMAN TUMOR XENOGRAFTS; ANTITUMOR-ACTIVITY; PHASE-II; CAMPTOTHECIN; PHARMACOKINETICS; NEUROBLASTOMA; ETOPOSIDE; TOPOTECAN; EFFICACY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
G. Vassal et al., "POTENT THERAPEUTIC ACTIVITY OF IRINOTECAN (CPT-11) AND ITS SCHEDULE DEPENDENCY IN MEDULLOBLASTOMA XENOGRAFTS IN NUDE-MICE", International journal of cancer, 73(1), 1997, pp. 156-163

Abstract

The anti-tumor activity of irinotecan (CPT-11), a DNA-topoisomerase 1inhibitor, was evaluated in 5 advanced stage subcutaneous medulloblastoma xenografts in nude mice, using different schedules of administration, With a 5-day schedule, the highest i.v. dose tested (40 mg kg(-1)day(-1)) induced complete regressions in all xenografts but 1, and delays in tumor growth always exceeded 30 days, Two xenografts, IGRM11 acid IGRM33, were highly sensitive, and animals survived tumor-free beyond 120 days after treatment, CPT-11 clearly retained its anti-tumor activity at a lower dosage (27 mg kg(-1) day(-1)), CPT-11 was significantly more active than cyclophosphamide, thiotepa and etoposide againstthe 3 xenografts evaluated, To study the schedule dependency of its anti tumor activity, CPT-11 was given i.v. at the same total doses overthe same period (33 days) using either a protracted or a sequential schedule in IGRM34-bearing mice. With a dose of 10 mg kg(-1) day(-1) given on days 0-4, days 7-11, days 21-25 and days 28-32 (total dose, 200mg kg(-1)), 3 of 6 animals were tumor free on day 378, The same totaldose given with a sequential schedule, i.e., 20 mg kg(-1) day(-1) on days 0-4 and days 28-32, failed to induce complete regression. The plasma pharmacokinetics of CPT-11 and SN-38 were studied in IGRM34-bearing animals after a single i.v. dose of 10 and 40 mg kg(-1). The plasma clearance rate of CPT-11 was dose dependent. The ratio between the SN-38 and CPT-11 area under the curve in plasma was 0.4-0.65, i.e., significantly higher than that observed in humans at the maximum tolerated dose (0.01-0.05), Conversely, this ratio was 10-fold lower in tumor than in plasma, Clinical development of irinotecan is warranted in pediatric malignancies. (C) 1997 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 02:15:55