RESPONSE OF HUMAN TUMOR XENOGRAFTS IN ATHYMIC NUDE-MICE TO DOCETAXEL (RP-56976, TAXOTERE(R))

被引:47
作者
DYKES, DJ [1 ]
BISSERY, MC [1 ]
HARRISON, SD [1 ]
WAUD, WR [1 ]
机构
[1] RHONE POULENC RORER SA,F-94403 VITRY,FRANCE
关键词
TAXOTERE(R); DOCETAXEL; HUMAN TUMOR XENOGRAFTS; CHEMOTHERAPY;
D O I
10.1007/BF02614214
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Docetaxel (Taxotere(R), RP 56976, NSC 628503), a new taxoid, was evaluated for preclinical evidence of anticancer activity in athymic nude (NCr-nu) mice bearing established, subcutaneously (s.c.) implanted human tumor xenografts CX-1 or KM20L2 (colon carcinomas), LX-1 (lung carcinoma), MX-1 (mammary carcinoma), and SK-MEL-2 (melanoma). Other evaluations used OVCAR-3 (ovarian carcinoma) xenografts implanted intraperitoneally (i.p.). Docetaxel was administered intravenously (i.v.) every 4 days for 3 injections (q4d x 3) except for one OVCAR-3 experiment in which the drug was given i.p. every 7 days for 3 injections. Tumor measurements, animal body weights, and mortality were determined. The highest dosage used (50 mg/kg/dose) was toxic in all experiments in which the 4-day treatment interval was used. The maximally tolerated dosage (MTD) ranged from 15 to 33 mg/kg/dose. Therapeutic responses among these xenografts ranged from clinically important long-term tumor-free survivors (MX-1, SK-MEL-2, and OVCAR-3) to tumor growth delays of various durations (CX-1, LX-1, and KM20L2). The response of SK-MEL-2, a xenograft highly refractory to available drugs, was particularly noteworthy. These results are indicative of a broad spectrum of antitumor activity for docetaxel.
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页码:1 / 11
页数:11
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