Synergistic antitumoral activity of combined UFT, folinic acid and oxaliplatin against human colorectal HT29 cell xenografts in athymic nude mice

Abstract

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.

Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells

“…Besides two transactivating elements identified in the PSTI promoter gene, including IL-6 and AP-1 Yasuda et al, 1993), another regulatory sequence functions positively in pancreatic cells but as negative active element in nonpancreatic cells (Yasuda et al, 1998). In that respect, we cannot exclude the possibility that methotrexate and 5-FU-based combination chemotherapy (Louvet et al, 2000;Andre et al, 2004;Poole et al, 2006) might have the ability to upregulate the expression of the TATI gene through several mechanisms including aberrant expression of differentiationassociated phenotypes, and to influence the invasive and metastatic potential of growing tumors in a subset of breast and colon cancer patients.…”

Antitumor Efficacy of Edotecarin as a Single Agent and in Combination with Chemotherapy Agents in a Xenograft Model

“…As a general principle, 70% of the maximum tolerated dose of the second drug was combined with edotecarin. The 5-FU dose was 50 mg/kg based on maximum tolerated dose reported by Houghton et al (20), the irinotecan dose was 45 mg/kg as described previously (26), the cisplatin dose of 5 mg/kg was estimated from Keane et al (21), the oxaliplatin dose was 10 mg/kg as described previously (27,28), and the SU-11248 doses of 20 and 40 mg/kg were based on data from preclinical studies (23 -25). Edotecarin was dissolved in 20% polyethylene glycol 400 and water.…”

A multiple-center phase II study of biweekly oxaliplatin and tegafur–uracil/leucovorin for chemonaive patients with advanced gastric cancer

“…In a pilot study, patients with advanced scirrhous-type gastric cancer who were given preoperative OXA showed a clinical response with signiWcant platinum concentration observed in tissue examined postoperatively [15]. The combination of OXA, oral tegafur-uracil and LV has shown synergistic antitumor activity against human colorectal HT29 cell xenografts in athymic nude mice [16]. To date, few data have been collected from phase I and II clinical studies investigating the use of OXA combining oral tegafur-uracil and LV in patients with gastric cancer.…”