Skip to main content
main-content

14.06.2016 | Original Article | Ausgabe 2/2016

Cancer Chemotherapy and Pharmacology 2/2016

A Phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, -2, and -3 tyrosine kinases in Chinese patients with advanced solid tumors

Zeitschrift:
Cancer Chemotherapy and Pharmacology > Ausgabe 2/2016
Autoren:
Junning Cao, Jian Zhang, Wei Peng, Zhiyu Chen, Songhua Fan, Weiguo Su, Ke Li, Jin Li
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00280-016-3069-8) contains supplementary material, which is available to authorized users.

Abstract

Purpose

Fruquintinib (HMPL-013) is a novel oral small molecule compound that selectively inhibits vascular endothelial growth factor receptors-1, -2, and -3 with potent inhibitory effects on multiple human tumor xenografts. This first-in-human study was conducted to assess the maximum tolerated dose and dose-limiting toxicities, safety and tolerability, pharmacokinetics, and preliminary anti-tumor activity of fruquintinib.

Methods

Patients 18–70 years old with advanced solid tumors refractory to standard therapies were recruited. Fruquintinib was administered orally in 4-week repeating cycles in two regimens, either once daily continuously or once daily for 3-week on/1-week off, until discontinuation due to toxicity or tumor progression. Adverse events were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.3. Pharmacokinetic parameters were measured after a single dose and in multiple dosing. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors v1.0.

Results

Forty patients were enrolled into 5 cohorts in continuous regimen and 2 cohorts in 3-week-on/1-week-off regimen. The most common grade 3/4 adverse events were hand–foot skin reaction, hypertension, and thrombocytopenia. PK analysis showed good and rapid absorption followed by slow terminal elimination with a mean half-life of approximately 42 h which was consistent across all dose groups. Thirty-four patients were evaluable for tumor response, including 14 with partial response and 14 with stable disease.

Conclusions

Fruquintinib showed an acceptable safety profile and preliminary evidence of anti-tumor activity in patients with advanced solid tumors. The recommended dose was determined to be either 4 mg QD on a continuous regimen or 5 mg QD on a 3-week-on/1-week-off regimen.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Bis zum 22.10. bestellen und 100 € sparen!

Weitere Produktempfehlungen anzeigen
Zusatzmaterial
Supplementary material 1 (DOCX 19 kb)
280_2016_3069_MOESM1_ESM.docx
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 2/2016

Cancer Chemotherapy and Pharmacology 2/2016Zur Ausgabe
  1. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

  2. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

Neu im Fachgebiet Onkologie

 

 

 
 

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Onkologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise