Dataset Information

Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients.

ABSTRACT:

Background

Axitinib is an oral, potent and selective inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3. We report on data obtained from 18 Japanese patients with advanced solid tumors in two phase I trials that evaluated the safety, pharmacokinetics and antitumor activity of axitinib and also examined potential biomarkers.

Methods

Six patients received a single 5-mg dose of axitinib followed by 5 mg twice daily (BID), and an additional six patients received axitinib 5 mg BID only. Another six patients received axitinib at 5-mg, 7-mg and 10-mg single doses followed by 5 mg BID.

Results

Plasma pharmacokinetics following single doses of axitinib was generally linear. Common treatment-related adverse events were fatigue (83%), anorexia (72%), diarrhea (67%), hand-foot syndrome (67%) and hypertension (61%). Sixteen patients (89%) experienced thyroid-stimulating hormone (TSH) elevation. Grade 3/4 toxicities included hypertension (33%) and fatigue (28%). No grade 3/4 fatigue occurred in patients who started thyroid hormone replacement therapy when TSH was elevated. Thyroglobulin elevation was observed in all patients who continued treatment with axitinib for ?3 months. Abnormal TSH correlated with exposure to axitinib (r?=?0.72). Decrease in soluble (s) VEGFR-2 levels significantly correlated with exposure to axitinib (r?=?-0.94). Axitinib showed antitumor activity across multiple tumor types.

Conclusions

Axitinib-related thyroid dysfunction could be due to a direct effect on the thyroid gland. Grade 3/4 fatigue and hypothyroidism appear to be controllable with use of thyroid hormone replacement therapy. sVEGFR-2 and TSH may act as biomarkers of axitinib plasma exposure.

SUBMITTER: Fujiwara Y

PROVIDER: S-EPMC3348450 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients.

Fujiwara Yutaka Y Kiyota Naomi N Chayahara Naoko N Suzuki Akiyuki A Umeyama Yoshiko Y Mukohara Toru T Minami Hironobu H

Investigational new drugs 20110208 3

<h4>Background</h4>Axitinib is an oral, potent and selective inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3. We report on data obtained from 18 Japanese patients with advanced solid tumors in two phase I trials that evaluated the safety, pharmacokinetics and antitumor activity of axitinib and also examined potential biomarkers.<h4>Methods</h4>Six patients received a single 5-mg dose of axitinib followed by 5 mg twice daily (BID), and an additional six patients rece ...[more]

PMID: 21301929

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Dataset Information

Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients.

Background

Methods

Results

Conclusions

Publications

Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients.

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