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Titolo:
PHASE-I AND PHARMACOKINETIC STUDY OF THE CAMPTOTHECIN DERIVATIVE IRINOTECAN, ADMINISTERED ON A WEEKLY SCHEDULE IN CANCER-PATIENTS
Autore:
DEFORNI M; BUGAT R; CHABOT GG; CULINE S; EXTRA JM; GOUYETTE A; MADELAINE I; MARTY ME; MATHIEUBOUE A;
Indirizzi:
HOP ST LOUIS,DEPT MED ONCOL,1 AVE CLAUDE VELLEFAUX F-75010 PARIS FRANCE HOP ST LOUIS,DEPT MED ONCOL F-75010 PARIS FRANCE INST GUSTAVE ROUSSY,CLIN PHARMACOL LAB,CNRS,URA 147 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,INSERM,U140 F-94805 VILLEJUIF FRANCE LAB ROGER BELLON NEUILLY SUR SEINE FRANCE CTR CLAUDIUS REGAUD TOULOUSE FRANCE
Titolo Testata:
Cancer research
fascicolo: 16, volume: 54, anno: 1994,
pagine: 4347 - 4354
SICI:
0008-5472(1994)54:16<4347:PAPSOT>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA TOPOISOMERASE-I; CELL LUNG-CANCER; ANTITUMOR-ACTIVITY; MAMMALIAN DNA; MURINE TUMORS; ANALOG CPT-11; L1210 CELLS; NSC-100880; MECHANISM; DRUG;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
55
Recensione:
Indirizzi per estratti:
Citazione:
M. Deforni et al., "PHASE-I AND PHARMACOKINETIC STUDY OF THE CAMPTOTHECIN DERIVATIVE IRINOTECAN, ADMINISTERED ON A WEEKLY SCHEDULE IN CANCER-PATIENTS", Cancer research, 54(16), 1994, pp. 4347-4354

Abstract

Irinotecan (CPT-11) is a novel water-soluble, semisynthetic derivative of camptothecin, with inhibitory effects on mammalian DNA topoisomerase I, high cytotoxic activity in vitro and anticancer activity in animal models. Fifty-nine patients, with cancer refractory to conventional therapy, were entered in this phase I study, using a weekly scheduleadministration. A total of 304 weekly doses were administered at doselevels ranging from 50 to 145 mg/m(2) (30-90 min i.v. infusion). Leukoneutropenia and diarrhea were the dose-limiting toxicities and appeared to be dose related, reversible and noncumulative. However, interpatient variability of toxic effects was substantial. Prolongation of theinfusion time from 30 min to 90 min appeared to decrease the diarrhea. Other toxicities included moderate emesis, asthenia, alopecia, abdominal pain, and anemia. CPT-11 plasma disposition was bi- or triphasic with a terminal half-life of 9.3 h. CPT-11 area under the plasma concentration versus time curves increased linearly with dose (r = 0.47, P < 0.01). The active metabolite area under the plasma concentration versus time curve correlated significantly with that of CPT-11, but not with that of CPT-11 dose. Both CPT-11 and 7-ethyl-10-hydroxycamptothecin areas under the plasma concentration versus time curve correlated significantly with leukoneutropenia and diarrhea. One partial and 4 minor responses were observed at dose levels of 130 and 145 mg/m(2). Usingthis weekly schedule, recommended doses for phase II studies are 100 mg/m(2) in high risk patients and 115 mg/m(2) in others.

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Documento generato il 25/11/20 alle ore 15:56:53