Dykes D J, Bissery M C, Harrison S D, Waud W R
Southern Research Institute, Birmingham, AL 35255, USA.
Invest New Drugs. 1995;13(1):1-11. doi: 10.1007/BF02614214.
Docetaxel (Taxotere, 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.
多西他赛（泰索帝，RP 56976，NSC 628503）是一种新型紫杉烷类药物，我们对其在携带已建立的皮下植入人肿瘤异种移植物CX-1或KM20L2（结肠癌）、LX-1（肺癌）、MX-1（乳腺癌）和SK-MEL-2（黑色素瘤）的无胸腺裸（NCr-nu）小鼠中的抗癌活性进行了临床前证据评估。其他评估使用腹腔内（i.p.）植入的OVCAR-3（卵巢癌）异种移植物。多西他赛每4天静脉注射（i.v.）一次，共注射3次（q4d×3），但有一个OVCAR-3实验中，药物每7天腹腔注射一次，共注射3次。测定肿瘤大小、动物体重和死亡率。在所有采用4天治疗间隔的实验中，所用的最高剂量（50 mg/kg/剂量）均有毒性。最大耐受剂量（MTD）范围为15至33 mg/kg/剂量。这些异种移植物中的治疗反应范围从临床上重要的长期无瘤存活者（MX-1、SK-MEL-2和OVCAR-3）到不同持续时间的肿瘤生长延迟（CX-1、LX-1和KM20L2）。对现有药物高度耐药的异种移植物SK-MEL-2的反应尤其值得注意。这些结果表明多西他赛具有广泛的抗肿瘤活性。
