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

C K Hoh, H A Burris 3rd, J C Bendell, J Tarazi, B Rosbrook, S Kim, J R Infante, T R Reid, C K Hoh, H A Burris 3rd, J C Bendell, J Tarazi, B Rosbrook, S Kim, J R Infante, T R Reid

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.

Figures

Figure 1
Figure 1
Duration of axitinib treatment.
Figure 2
Figure 2
Median progression-free survival for patients with colorectal cancer (n=17). Abbreviations: CI=confidence interval; mPFS=median progression-free survival.
Figure 3
Figure 3
Patient level (A) SUVmax scores (n=18) and (B) maximum Kpat values (n=13; 5 patients were missing baseline or follow-up measurements); percentage change from baseline in (C) SUVmax scores (n=18) and (D) maximum Kpat values (n=12).aSUVmean scores and average Kpat values shown for the five patients with liver lesions. Abbreviations: Kpat=Patlak influx constant; SUV=standardised uptake value.
Figure 4
Figure 4
Changes in 18FLT uptake during and after axitinib treatment in a 3.0 × 3.1 cm2 right ilio-sacral region mass in a sample patient. Arrows denote site of target lesion at (A) baseline; (B) day 7 axitinib dosing; (C) day 10 (3 days after stopping axitinib dose); (D) day 14 (7 days after stopping axitinib); and (E) computed tomography slide of corresponding region of reference. Abbreviations: 18FLT= [18F] fluorothymidine; Kpat=Patlak influx constant; SUVmax=maximum uptake value.

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Source: PubMed

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