• F A L M Eskens, P Tresca, D Tosi, L Van Doorn, H Fontaine, A Van der Gaast, C Veyrat-Follet, C Oprea, M Hospitel, and V Dieras.
• Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
• Br. J. Cancer. 2014 Apr 29; 110 (9): 2170-7.

BackgroundThe vascular disrupting agent ombrabulin shows synergy with docetaxel in vivo. Recommended phase II doses were determined in a dose escalation study in advanced solid tumours.MethodsOmbrabulin (30-min infusion, day 1) followed by docetaxel (1-h infusion, day 2) every 3 weeks was explored. Ombrabulin was escalated from 11.5 to 42 mg m(-2) with 75 mg m(-2) docetaxel, then from 30 to 35 mg m(-2) with 100 mg m(-2) docetaxel. Recommended phase II dose cohorts were expanded.ResultsFifty-eight patients were treated. Recommended phase II doses were 35 mg m(-2) ombrabulin with 75 mg m(-2) docetaxel (35/75 mg m(-2); 13 patients) and 30 mg m(-2) ombrabulin with 100 mg m(-2) docetaxel (30/100 mg m(-2); 16 patients). Dose-limiting toxicities were grade 3 fatigue (two patients; 42/75, 35/100), grade 3 neutropaenic infection (25/75), grade 3 headache (42/75), grade 4 febrile neutropaenia (30/100), and grade 3 thrombosis (35/100). Toxicities were consistent with each agent; mild nausea/vomiting, asthaenia/fatigue, alopecia, and anaemia were common, as were neutropaenia and leukopaenia. Diarrhoea, nail disorders and neurological symptoms were frequent at 100 mg m(-2) docetaxel. Pharmacokinetic analyses did not show any relevant drug interactions. Ten patients had partial responses (seven at 30 mg m(-2) ombrabulin), eight lasting >3 months.ConclusionsSequential administration of ombrabulin with 75 or 100 mg m(-2) docetaxel every 3 weeks is feasible.

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