• Robert L Coleman, James Moon, Anil K Sood, Wei Hu, James E Delmore, Albert J Bonebrake, Garnet L Anderson, Setsuko K Chambers, and Maurie Markman.
• University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA. Electronic address: rcoleman@mdanderson.org.
• Eur. J. Cancer. 2014 Jun 1;50(9):1638-48.

BackgroundVandetanib is an oral tyrosine kinase inhibitor of VEGFR-2/3, EGFR and RET, which has demonstrated clinical activity as a single agent and in combination with taxanes. We explored the efficacy, safety and toxicity of docetaxel and vandetanib in women with recurrent ovarian cancer (OC).MethodsWomen with refractory or progressive OC were randomised 1:1 to docetaxel (75 mg/m(2), IV)+vandetanib (100mg daily, PO, D+V) or docetaxel (75 mg/m(2), D). Up to three additional cytotoxic regimens for recurrence and prior anti-angiogenic agents (as primary therapy) were allowed. The primary end-point was progression free survival (PFS). The study had 84% power to detect a PFS hazard ratio of 0.65, using a one-sided P of 0.1. This corresponds to an increase in median PFS from 3.6 months to 5.6 months. Patients progressing on D were allowed to receive single agent vandetanib (D → V).Results131 Patients were enrolled; two were excluded. 16% had received prior anti-angiogenic therapy. The median PFS estimates were 3.0 mos (D+V) versus 3.5 (D); HR: 0.99 (80% CI: 0.79-1.26). 61 Patients on D+V were assessable for toxicity; 20(33%) had treatment-related Grade (G) 4 events, primarily haematologic. Similarly, 17 (27%) of 64 patients receiving D had G4 events, primarily haematologic. 27 Evaluable patients crossed-over to V. 1/27(4%) experienced a G4 event. G3 diarrhoea was observed in 4% D → V patients. Median OS was 14 mos (D+V) versus 18 mos (D → V); HR(OS): 1.25 (80% CI: 0.93-1.68). Crossover vandetanib response was 4% (1/27 evaluable patients). High plasma IL-8 levels were associated with response to D+V.ConclusionsCombination docetaxel+vandetanib did not prolong PFS relative to docetaxel alone in OC patients. No unexpected safety issues were identified.Copyright © 2014 Elsevier Ltd. All rights reserved.

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