Phase I study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with 5-fluorouracil and leucovorin: A safe combination
European Journal of Cancer , Volume 42 - Issue 4 p. 467- 472
We performed a phase I study with the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 combined with 5-fluorouracil and leucovorin (5-FU/LV) to determine safety profile and assess pharmacokinetic interactions. Patients with advanced solid malignancies received LV 20 mg/m2 followed by 5-FU 425 mg/m2 both administered intravenously in 15 min daily for 5 days every 4 weeks. ABT-510 was administered subcutaneously twice daily continuously from day 2 onwards. Blood and urine samples for pharmacokinetic analyses were collected at days 1, 5 and 22. Twelve patients received a total of 45 cycles of 5-FU/LV combined with ABT-510. ABT-510 dose levels studied were 50 and 100 mg. The combination was well tolerated, with a toxicity profile comparable to that of 5-FU/LV alone. At the dose levels studied no significant pharmacokinetic interactions were observed. These data indicate that ABT-510 administered twice daily subcutaneously can be safely combined with 5-FU/LV administered daily for 5 days, every 4 weeks.
|ABT-510, Angiogenesis inhibitors, Clinical trial, Fluorouracil, Phase I, Thrombospondin 1|
|European Journal of Cancer|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Hoekstra, R, Gietema, J.A, de Vos, F.Y.F.L, Eskens, F.A.L.M, de Vries, E.G.E, Uges, D.R.A, … Verweij, J. (2006). Phase I study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with 5-fluorouracil and leucovorin: A safe combination. European Journal of Cancer, 42(4), 467–472. doi:10.1016/j.ejca.2005.08.040