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Br J Cancer. 2014 Feb 18;110(4):875-81. doi: 10.1038/bjc.2013.806. Epub 2014 Jan 14.

Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours.

Author information

1
Department of Radiology, University of California San Diego, San Diego, CA, USA.
2
Sarah Cannon Research Institute and Tennessee Oncology PLLC, Nashville, TN, USA.
3
Pfizer Oncology, San Diego, CA, USA.
4
Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.

Abstract

BACKGROUND:

We evaluated week-on/week-off axitinib dosing plus chemotherapy in patients with gastrointestinal tumours, including tumour thymidine uptake by fluorine-18 3'-deoxy-3'-fluorothymidine positron emission tomography ((18)FLT-PET).

METHODS:

During a lead-in period, patients received twice daily (b.i.d.) axitinib 7 mg (n=3) or 10 mg (n=18) for 7 days followed by a 7-day dosing interruption; serial (18)FLT-PET scans were performed before day 1 and on days 7, 10, and 14. Axitinib plus FOLFIRI or FOLFOX was then administered in 2-week cycles; axitinib was interrupted on day 10 of each cycle for 7 days.

RESULTS:

The maximum tolerated dose of axitinib was 10 mg b.i.d., in a week-on/week-off schedule, combined with FOLFIRI or FOLFOX. Common all-causality grade 3 adverse events were neutropenia (38%), hypertension (33%), and fatigue (29%). Of 21 patients, 2 (10%) had a partial response and 12 (57%) had stable disease. Following 7 days of continuous axitinib dosing, tumour (18)FLT uptake decreased -49% from baseline and recovered to -28% and -17% from baseline, respectively, after 3 and 7 days of axitinib interruption.

CONCLUSION:

Axitinib administered in a week-on/week-off schedule combined with FOLFIRI or FOLFOX is supported by (18)FLT-PET data and was well tolerated in patients with gastrointestinal tumours.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00460603.

PMID:
24423921
PMCID:
PMC3929885
DOI:
10.1038/bjc.2013.806
[Indexed for MEDLINE]
Free PMC Article

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