Synergistic antitumoral activity of combined UFT, folinic acid and oxaliplatin against human colorectal HT29 cell xenografts in athymic nude mice.
This study was designed to assess the inhibition of tumor growth by oxaliplatin combined with UFT and folinic acid (FA). Growth inhibition was studied in nude mice transplanted with human colorectal HT29 tumor cell xenografts and treated for 28 days with oral UFT (20 mg/kg/day) and FA (4 mg/kg/day), i.p. oxaliplatin (10 mg/kg on day 1) or a combination of oxaliplatin, UFT and FA, or else not treated (controls). Tumor surface area and weight were recorded twice a week, and mice were sacrificed at day 28. Two separate experiments were performed for each group of 25 mice. At day 28, mean tumor weights (g) were 2.89+/-0.22 (controls), 2.03+/-0.14 (oxaliplatin), 2.02+/-0.21 (UFT/FA) and 1.23+/-0.17 (oxaliplatin+UFT/FA). For the three treatment groups, tumor weight decreases were 30.1% (p<0.05), 29.9% (p<0.05) and 57.5% (p<0.001), respectively. Combined treatment (UFT/FA+oxaliplatin) reduced tumor weight by 39% compared to oxaliplatin alone (p<0.05) or UFT/FA (p<0.05). These results demonstrate the synergistic effect of the combination of oxaliplatin, UFT and FA in this HT29 cell xenograft model, and warrant further investigations in patients with metastatic colorectal cancer.
Louvet
C
C
INSERM Unit 482, Hôpital St-Antoine, Paris, France. christophe.louvet@sat.ap-hop-paris.fr
Coudray
A M
AM
Tournigand
C
C
Prévost
S
S
Raymond
E
E
de Gramont
A
A
Chazard
M
M
Gespach
C
C
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D019073:HT29 Cells; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014498:Uracil / Q000009:adverse effects / Q000627:therapeutic use*
D004338:Drug Combinations; D009944:Organoplatinum Compounds; C096910:UFT(R) drug; D000077150:Oxaliplatin; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin