Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-10

AUTHORS

L P Martin, M F Kozloff, R S Herbst, T A Samuel, S Kim, B Rosbrook, M Tortorici, Y Chen, J Tarazi, A J Olszanski, T Rado, A Starr, R B Cohen

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. More... »

PAGES

1268

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2012.407

DOI

http://dx.doi.org/10.1038/bjc.2012.407

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1025415738

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22996612


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