Evidence map›Paper›PMID 21301929›Full record

ArticleInvestigational new drugs2012

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

Yutaka Fujiwara, Naomi Kiyota, Naoko Chayahara, Akiyuki Suzuki, Yoshiko Umeyama, Toru Mukohara, Hironobu Minami

Open access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
6.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.

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  19. Population pharmacokinetic analysis of axitinib in healthy volunteers.British journal of clinical pharmacology · 2014
    Article
  20. Clinical pharmacology of axitinib.Clinical pharmacokinetics · 2013
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Yutaka FujiwaraMedical Oncology/Hematology, Department of Medicine, Kobe University Hospital, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. yufujiwa@med.kobe-u.ac.jp
Naomi Kiyota
Naoko Chayahara
Akiyuki Suzuki
Yoshiko Umeyama
Toru Mukohara
Hironobu Minami
Kobe University Hospital · JPPfizer (Japan) · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAxitinib 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.

methodsSix 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.

resultsPlasma 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.

conclusionsAxitinib-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.

Indexed as

AdultAgedAngiogenesis InhibitorsAsian PeopleAxitinibBiomarkersFatigueFemaleHumansHyperthyroidismHypothyroidismImidazolesIndazolesMaleMiddle AgedNeoplasmsAngiogenesis InhibitorsAxitinibBiomarkersImidazolesIndazolesProto-Oncogene Proteins c-kitThyroglobulinThyrotropinVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3VEGFA protein, human

Identifiers

PMID21301929
PMCPMC3348450
OpenAlexW2004465662

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.