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Clinical Trial
. 2012 Oct 9;107(8):1277-85.
doi: 10.1038/bjc.2012.406. Epub 2012 Sep 18.

Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours

M F Kozloff  1 , L P Martin, M Krzakowski, T A Samuel, T A Rado, E Arriola, J De Castro Carpeño, R S Herbst, J Tarazi, S Kim, B Rosbrook, M Tortorici, A J Olszanski, R B Cohen
Affiliations
Clinical Trial

Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours

M F Kozloff et al. Br J Cancer. .

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.

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Figures

Figure 1
Figure 1
Treatment schedule for (A) paclitaxel/carboplatin cohorts and (B) gemcitabine/cisplatin cohort. aChemotherapy (CT)=paclitaxel/carboplatin for cohort 1, 2 and 3. C=cycle; Cis=cisplatin; Gem=gemcitabine; PK=pharmacokinetic.
Figure 2
Figure 2
Duration of study treatment.
Figure 3
Figure 3
Plasma concentration–time curves for (A) axitinib, paclitaxel and carboplatin and (B) axitinib, gemcitabine and cisplatin. Abbreviation: PUF=plasma ultrafiltrate.
See this image and copyright information in PMC

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