The new dioxolane, (-)-2 '-deoxy-3 '-oxacytidine (BCH-4556, troxacitabine), has activity against pancreatic human tumor xenografts

There is a great need for new therapeutic agents for patients with advanced pancreatic cancer. The new dioxolane analogue troxacitabine was evaluated in two human pancreatic cancer xenograft models. The models used included t he Panc-01 and MiaPaCa pancreatic cancer cell, lines. Whereas there is cert ainly no absolute evidence that either of the in vivo models is predictive for clinical activity, there is at least some evidence that they may be hel pful in selecting agents for clinical trials in patients with pancreatic ca ncer. Troxacitabine was administered i.v. to the animals at doses of 10 and 25 mg/kg on a daily x 5 regimen. Gemcitabine was used as a positive contro l, The end points for the study included tumor growth inhibition (TGI), fin al weight, and the number of partial and complete tumor responses in the an imals, Troxacitabine was highly active against the Panc-01 model (n = 8), w ith TGI levels of 88.5% and 84.3% at the 10 and 25 mg/kg doses, respectivel y. The mean final tumor weights for animals given troxacitabine were also s ignificantly smaller (P < 0.001) compared with vehicle controls. At the 10 mg/kg dose, there were three partial tumor shrinkages and one complete tumo r shrinkage, whereas at the 25 mg/kg dose, there were three partial tumor s hrinkages. Troxacitabine had less activity against the MiaPaCa model (n = 1 0) and, by traditional response criteria, would be considered inactive, wit h TGIs of 4% and 22.7% at the 10 and 25 mg/kg dose level, respectively. Of note is that in comparison with gemcitabine, troxacitabine was more efficac ious against Panc-01 and was equally active against MiaPaCa. These in vivo results are encouraging and support the prospect of performing Phase II and perhaps Phase III trials with troxacitabine in patients with advanced panc reatic cancer.