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Martin LP , Kozloff MF , Herbst RS , Samuel TA , Kim S , Rosbrook B , Tortorici M , Chen Y , Tarazi J , Olszanski AJ , Rado T , Starr A , Cohen RB
Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours
British Journal of Cancer. 2012 Oct;107(8) :1268-1276
PMID: WOS:000309963100011    PMCID: PMC3494424   
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Abstract
BACKGROUND: Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, enhanced the efficacy of chemotherapy in human xenograft tumour models. This phase I study investigated the safety, tolerability, pharmacokinetics and antitumour activity of axitinib combined with chemotherapy. METHODS: A total of 42 patients with advanced solid tumours received a continuous axitinib starting dose of 5 mg twice daily (b.i.d.) plus paclitaxel (90 mg m(-2) weekly), docetaxel (100 mg m(-2) every 3 weeks) or capecitabine (1000 or 1250 mg m(-2) b.i.d., days 1-14). RESULTS: Common treatment-related adverse events across all cohorts were nausea (45.2%), hypertension (45.2%), fatigue (42.9%), diarrhoea (38.1%), decreased appetite (33.3%) and hand-foot syndrome (31.0%). There was one complete response, nine partial responses and seven patients with stable disease. Ten patients (23.8%) remained on therapy for >8 months. Paclitaxel and capecitabine pharmacokinetics were similar in the absence or presence of axitinib, but docetaxel exposure was increased in the presence of axitinib. Axitinib pharmacokinetics were similar in the absence or presence of co-administered agents. CONCLUSIONS: Axitinib combined with paclitaxel or capecitabine was well tolerated; no additive increase in toxicities was observed. Antitumour activity was observed for each treatment regimen and across multiple tumour types. British Journal of Cancer (2012) 107, 1268-1276. doi:10.1038/bjc.2012.407 www.bjcancer.com Published online 20 September 2012 (C) 2012 Cancer Research UK
Notes
Martin, L. P. Kozloff, M. F. Herbst, R. S. Samuel, T. A. Kim, S. Rosbrook, B. Tortorici, M. Chen, Y. Tarazi, J. Olszanski, A. J. Rado, T. Starr, A. Cohen, R. B. Pfizer Inc.; National Cancer Institute [5P30CA006927] This study was sponsored by Pfizer Inc. Additional support was provided to Fox Chase Cancer Center by Grant 5P30CA006927 from the National Cancer Institute. We thank the patients who participated in this study and the physicians who referred them as well as the study coordinators and data managers, Shelley Mayfield and Carol Martins at Pfizer Inc., for support of the study conduct and Gamal ElSawah, Pfizer Medical Affairs, for his review of the manuscript. Medical writing support was provided by Joanna Bloom of UBC Scientific Solutions (Southport, CT, USA) and Christine Arris of ACUMED (Tytherington, UK) and was funded by Pfizer Inc. 35 Nature publishing group London 022mi