A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with gemcitabine and cisplatin in patients with solid tumors
Annals of Oncology , Volume 17 - Issue 8 p. 1320- 1327
Background: The aim of the study was to determine the safety profile, pharmacokinetics and potential drug interactions of the angiogenesis inhibitor ABT-510 combined with gemcitabine - cisplatin chemotherapy in patients with solid tumors. Patients and methods: Patients with advanced solid tumors received gemcitabine 1250 mg/m 2 intravenously (i.v.) on days 1 and 8 and cisplatin 80 mg/m 2 on day 1 of a 3-week cycle in combination with ABT-510. ABT-510 was administered subcutaneously twice daily at doses of 50 mg or 100 mg. Plasma samples for pharmacokinetics were obtained on days 1 (gemcitabine, cisplatin as single agents), 15 (ABT-510 as single agent) and 22 (gemcitabine, cisplatin and ABT-510 as combination). Results: Thirteen patients received ABT-510 as either 50 mg b.i.d. (seven patients) or 100 mg b.i.d. (six patients) in combination with gemcitabine - cisplatin. The most common reported adverse events reflected the known toxicity profile induced by gemcitabine - cisplatin without ABT-510. One episode of hemoptysis occurred in a patient with non-small-cell lung cancer (NSCLC) after 13 days of treatment. No clinically significant pharmacokinetic interactions between ABT-510, gemcitabine and platinum were observed. Three partial responses were observed in 12 evaluable patients (one head and neck cancer, one melanoma and one NSCLC). Conclusions: Combining ABT-510 at doses of 50 mg and 100 mg with gemcitabine - cisplatin is feasible. Pharmacokinetic interactions were not observed and adding ABT-510 does not appear to increase toxicity.
|, , , ,|
|Annals of Oncology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Gietema, J.A, Hoekstra, R, de Vos, F.Y.F.L, Uges, D.R.A, van der Gaast, A, Groen, H.J.M, … Eskens, F.A.L.M. (2006). A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with gemcitabine and cisplatin in patients with solid tumors. Annals of Oncology, 17(8), 1320–1327. doi:10.1093/annonc/mdl102