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Kozloff MF , Martin LP , Krzakowski M , Samuel TA , Rado TA , Arriola E , De Castro Carpeno J , Herbst RS , Tarazi J , Kim S , Rosbrook B , Tortorici M , Olszanski AJ , Cohen RB
Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours
Br J Cancer. 2012 Oct 9;107(8) :1277-85
PMID: 22990652    PMCID: PMC3494447    URL: https://www.ncbi.nlm.nih.gov/pubmed/22990652
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Abstract
BACKGROUND: This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. METHODS: In all, 49 patients received axitinib 5 mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin. RESULTS: Two patients experienced dose-limiting toxicities: febrile neutropenia (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade >/=3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination. CONCLUSION: Axitinib 5 mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug-drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.
Notes
Kozloff, M F Martin, L P Krzakowski, M Samuel, T A Rado, T A Arriola, E De Castro Carpeno, J Herbst, R S Tarazi, J Kim, S Rosbrook, B Tortorici, M Olszanski, A J Cohen, R B eng P30 CA006927/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):1277-85. doi: 10.1038/bjc.2012.406. Epub 2012 Sep 18.