Annals of Oncology Advance Access originally published online on May 25, 2006
Annals of Oncology 2006 17(8):1320-1327; doi:10.1093/annonc/mdl102
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© 2006 European Society for Medical Oncology
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
Departments of 1 Medical Oncology, 3 Pharmacy and 4 Pulmonology, University of Groningen and University Medical Center Groningen, Groningen; 2 Department of Medical Oncology, Erasmus MC, Rotterdam, the Netherlands; 5 Abbott Laboratories, Chicago, IL, USA
* Correspondence to: Dr J. A. Gietema, Department of Medical Oncology, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, the Netherlands. Tel: +31-50-3611847; Fax: +31-50-3614862; E-mail: j.a.gietema{at}int.umcg.nl
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/m2 intravenously (i.v.) on days 1 and 8 and cisplatin 80 mg/m2 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.
Key words: ABT-510, angiogenesis inhibitor, cisplatin, gemcitabine, phase I