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Titolo:
PHARMACOKINETICS AND ANTITUMOR EFFECTS OF MITOXANTRONE AFTER INTRATUMORAL OR INTRAARTERIAL HEPATIC ADMINISTRATION IN RABBITS
Autore:
RAMIREZ LH; ZHAO ZX; ROUGIER P; BOGNEL C; DZODIC R; VASSAL G; ARDOUIN P; GOUYETTE A; MUNCK JN;
Indirizzi:
INST GUSTAVE ROUSSY,DEPT MED,RUE CAMILLE DESMOULINS F-94805 VILLEJUIFFRANCE INST GUSTAVE ROUSSY,DEPT MED F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,SERV EXPERIMETAT ANIM F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,LAB PHARMACOTOXICOL & PHARMACOGENET,CNRS,URA 147 F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT PATHOL ANAT F-94805 VILLEJUIF FRANCE
Titolo Testata:
Cancer chemotherapy and pharmacology
fascicolo: 4, volume: 37, anno: 1996,
pagine: 371 - 376
SICI:
0344-5704(1996)37:4<371:PAAEOM>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERCUTANEOUS ETHANOL INJECTION; HEPATOCELLULAR-CARCINOMA; ARTERIAL INFUSION; COLORECTAL-CANCER; RANDOMIZED TRIAL; OVARIAN-CANCER; II TRIAL; LIVER; TUMOR; CHEMOTHERAPY;
Keywords:
MITOXANTRONE; INTRATUMORAL INJECTIONS; EXPERIMENTAL LIVER TUMORS; PHARMACOKINETICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
L.H. Ramirez et al., "PHARMACOKINETICS AND ANTITUMOR EFFECTS OF MITOXANTRONE AFTER INTRATUMORAL OR INTRAARTERIAL HEPATIC ADMINISTRATION IN RABBITS", Cancer chemotherapy and pharmacology, 37(4), 1996, pp. 371-376

Abstract

The intratumoral (i.t.) delivery of anticancer drugs aims at controlling tumor growth and thereby provides palliative treatment for liver neoplasms. Mitoxantrone is a good candidate for local or regional administration because (1) its metabolism is mainly hepatic, (2) it has a steep dose-response curve for multiple solid tumors, and (3) its fixation in tissues is sustained without vesicant effects after extravasation. We compared the tolerance, pharmacokinetics, and antitumor effects of mitoxantrone on hepatic VX2 tumors in rabbits treated with i.t. intraarterial hepatic (i.a.h.) or i.v. mitoxantrone, i.t. ethanol; or i.t. 0.9% NaCl and in control animals. Tumor growth rates (TGRs) were evaluated at 9 days after treatment. Myelosuppression was the limiting toxicity of i.v. mitoxantrone at 1.5 mg/kg (maximal tolerated dose, MTD), but neither i.t. nor i.a.h. administration led to hematologic toxicity at the same dose. The mitoxantrone retained in tumors after i.t. administration was seen as blue-stained areas of complete necrosis according to histologic analysis. Pharmacokinetic parameters showed a significantly decreased systemic exposure to the drug after both regional treatments, although the i.a.h. route appeared to have an edge over thei.t. route. TGRs were significantly reduced after i.t. mitoxantrone (81 +/- 62%), i.a.h. mitoxantrone (337 +/- 110%), and i.t. ethanol treatments (287 +/- 117%) as compared with control values (886 +/- 223%; p< 0.01). Treatment with i.v. mitoxantrone (816 +/- 132%) had no antitumor effect, nor did NaCl injections (868 +/- 116%). Mitoxantrone given i.t. induced the highest antitumor effects, resulting in a 3.5-fold reduction in TGRs as compared with i.a.h. mitoxantrone and i.t. ethanol treatments (p < 0.02). Treatment with i.t. mitoxantrone provided efficient antitumor therapy without producing major side effects. This method should be considered as palliative treatment for nonresectable liver tumors and other localized malignancies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 04:33:50