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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
Br J Cancer. 2012 Oct 9;107(8) :1268-76
PMID: 22996612    PMCID: PMC3494424    URL: https://www.ncbi.nlm.nih.gov/pubmed/22996612
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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.
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 eng P30 CA006927/CA/NCI NIH HHS/ 5P30CA006927/CA/NCI NIH HHS/ Clinical Trial, Phase I Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Br J Cancer. 2012 Oct 9;107(8):1268-76. doi: 10.1038/bjc.2012.407. Epub 2012 Sep 20.