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Titolo:
Phase I study of topotecan administered as a 21-day continuous infusion inchildren with recurrent solid tumors: A report from the Children's Cancer Group
Autore:
Frangoul, H; Ames, MM; Mosher, RB; Reid, JM; Krailo, MD; Seibel, NL; Shaw, DWW; Steinherz, PG; Whitlock, JA; Holcenberg, JS;
Indirizzi:
Childrens Canc Grp, Arcadia, CA 91066 USA Childrens Canc Grp Arcadia CA USA 91066 s Canc Grp, Arcadia, CA 91066 USA Childrens Hosp & Reg Med Ctr, Seattle, WA USA Childrens Hosp & Reg Med Ctr Seattle WA USA Reg Med Ctr, Seattle, WA USA Mayo Clin & Mayo Fdn, Dept Pharmacol, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn Rochester MN USA 55905 acol, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn, Dept Oncol, Rochester, MN 55905 USA Mayo Clin & MayoFdn Rochester MN USA 55905 ncol, Rochester, MN 55905 USA Childrens Natl Med Ctr, Washington, DC 20010 USA Childrens Natl Med Ctr Washington DC USA 20010 , Washington, DC 20010 USA Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA Mem Sloan Kettering Canc Ctr New York NY USA 10021 New York, NY 10021 USA Vanderbilt Univ, Med Ctr, Nashville, TN USA Vanderbilt Univ Nashville TN USA erbilt Univ, Med Ctr, Nashville, TN USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 12, volume: 5, anno: 1999,
pagine: 3956 - 3962
SICI:
1078-0432(199912)5:12<3956:PISOTA>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA TOPOISOMERASE-I; 24-HOUR CONTINUOUS-INFUSION; SYSTEMIC EXPOSURE; ACUTE-LEUKEMIA; CAMPTOTHECIN NSC-100880; INHIBITOR TOPOTECAN; XENOGRAFTS; TRIAL; PHARMACOKINETICS; PHARMACODYNAMICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Frangoul, H Childrens Canc Grp, POB 60012, Arcadia, CA 91066 USA ChildrensCanc Grp POB 60012 Arcadia CA USA 91066 CA 91066 USA
Citazione:
H. Frangoul et al., "Phase I study of topotecan administered as a 21-day continuous infusion inchildren with recurrent solid tumors: A report from the Children's Cancer Group", CLIN CANC R, 5(12), 1999, pp. 3956-3962

Abstract

The purpose of this study was to determine the toxicity, maximum tolerateddose, and pharmacokinetics of a 21-day continuous infusion of topotecan inchildren with relapsed solid tumors. Fifteen patients received 40 courses of continuous ambulatory infusions of topotecan every 28 days or when therewas resolution of hematological toxicity and any grade 2 or greater nonhematological toxicity, The starting dose was 0.4 mg/m(2)/day. Total topotecanlevels were measured on days 1, 7, 14, and 21, Three of four patients who received a starting dose of 0.4 mg/m(2)/day experienced dose-limiting myelosuppression. At the reduced dose of 0.3 mg/m(2)/day, only two of the seven patients experienced dose-limiting myelosuppression. Subsequently, four patients with more limited prior therapy were treated with 0.4 mg/m(2)/day; three had dose-limiting myelosuppression, Two patients with a dose-limiting toxicity at 0.4 mg/m(2)/day tolerated additional courses at 0.3 mg/m(2)/day. An equal number of patients had grade 4 neutropenia or thrombocytopenia, Other adverse events were rare, Two patients with ependymoma, one with rhabdomyosarcoma, and one with retinoblastoma metastatic to the brain had objective responses. The steady state plasma concentration and clearance of topotecan (Css) was achieved by day 1, Css in six patients dth complete data were 1.44 +/- 0.50 and 2.13 +/- 0.83 ng/ml at 0.3 and 0.4 mg/m(2)/day, respectively. Thus, a 21-day topotecan infusion was well-tolerated at 0.3 mg/m(2)/day. Myelosuppression was the dose-limiting toxicity at 0.4 mg/m(2)/day. The steady state and clearance of topotecan in this study are similar to those reported in adult patients.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 12:43:57