N-膦乙酰-L-天冬氨酸对顺铂单独及与5-氟-2'-脱氧尿苷联合应用时抗小鼠结肠癌26肿瘤活性的调节作用

Modulation of the antitumour activity of cisplatin alone and in combination with 5-fluoro-2'-deoxyuridine by N-phosphonacetyl-L-aspartate in murine colon carcinoma no. 26.

作者信息

Van Laar J A, Mayhew E G, Cao S, Durrani F A, Peters G J, Rustum Y M

机构信息

Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

出版信息

Eur J Cancer. 1995 Jun;31A(6):974-6. doi: 10.1016/0959-8049(95)00191-3.

DOI:10.1016/0959-8049(95)00191-3

PMID:7646931

Abstract

Modulation of the therapeutic efficacy of cisplatin (CDDP) and 5-fluoro-2'-deoxyuridine (FdUrd) alone and in combination with N-phosphonacetyl-L-aspartate (PALA) was evaluated in mice bearing colon carcinoma (C-26) using a weekly intravenous (i.v.) push schedule for 3 weeks. A non-toxic dose of PALA (100 mg/kg) was administered i.v. 24 h prior to the i.v. administration of CDDP +/- FdUrd. The maximum tolerated doses (MTD) of CDDP and FdUrd when used as a single agent were 9 and 400 mg/kg, respectively. In combination, however, the MTD of CDDP and FdUrd were 2.5 and 300 mg/kg, respectively. PALA did not significantly affect the MTD. PALA improved the antitumour activity of CDDP or FdUrd when used alone; however, the highest tumour response, 66% complete tumour regression, was achieved with a PALA modulation of CDDP and FdUrd in combination.

摘要

采用每周静脉推注给药方案，连续3周，在荷结肠癌（C-26）小鼠中评估单独使用顺铂（CDDP）和5-氟-2'-脱氧尿苷（FdUrd）以及二者与N-磷乙酰-L-天冬氨酸（PALA）联合使用时的治疗效果。在静脉注射CDDP±FdUrd前24小时，静脉注射无毒剂量的PALA（100 mg/kg）。CDDP和FdUrd单独作为单一药物使用时的最大耐受剂量（MTD）分别为9和400 mg/kg。然而，联合使用时，CDDP和FdUrd的MTD分别为2.5和300 mg/kg。PALA对MTD没有显著影响。单独使用时，PALA可提高CDDP或FdUrd的抗肿瘤活性；然而，联合使用CDDP和FdUrd并经PALA调节时，肿瘤反应最高，完全肿瘤消退率达66%。