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.
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.
Van Laar
J A
JA
Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Mayhew
E G
EG
Cao
S
S
Durrani
F A
FA
Peters
G J
GJ
Rustum
Y M
YM
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005467:Floxuridine / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D005467:Floxuridine; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D002945:Cisplatin; C025034:doxifluridine