Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 4, pp 981–990

A multi-histology trial of fostamatinib in patients with advanced colorectal, non-small cell lung, head and neck, thyroid, and renal cell carcinomas, and pheochromocytomas

  • Sook Ryun Park
  • Giovanna Speranza
  • Richard Piekarz
  • John J. Wright
  • Robert J. Kinders
  • Lihua Wang
  • Thomas Pfister
  • Jane B. Trepel
  • Min-Jung Lee
  • Sylvia Alarcon
  • Seth M. Steinberg
  • Jerry Collins
  • James H. Doroshow
  • Shivaani Kummar
Original Article

Abstract

Purpose

A multi-cohort phase II study of fostamatinib, an oral multi-kinase inhibitor, was conducted to determine the response rate in patients with advanced colorectal (CRC), thyroid, non-small cell lung, head and neck, and renal cell carcinomas, and pheochromocytomas.

Methods

Patients received 200 mg fostamatinib BID in 4-week cycles with response assessed every 2 cycles. Blood was collected for pharmacokinetic analysis and measurements of circulating tumor cells and circulating endothelial (progenitor) cells (CE(P)Cs).

Results

A total of 37 patients (22 CRC), median of 4 prior therapies, were enrolled. Due to toxicities in four of the first five patients, the study was amended to incorporate a dose escalation phase for each histology. The maximum-tolerated dose was established at 50 mg BID in CRC but was not established for the other cancers. Common grade 3/4 toxicities included transaminitis, hyperbilirubinemia, and hypertension. Pharmacokinetic profile was similar to previous reports. Seventy-three percent of CRC patients had liver involvement and 91 % had prior anti-angiogenic therapy. Patients with abnormal liver tests at baseline were more likely to experience grade ≥2 hepatotoxicity than those with normal tests (44 vs. 0 %). No responses were observed; disease stabilization rate was 27 % in CRC. Reduction in CECs following treatment was associated with a better disease stabilization rate (75 vs. 0 %) in CRC.

Conclusion

Fostamatinib had limited anti-tumor activity in this first clinical trial in patients with advanced refractory solid tumors; reduction in CECs and CEPs was indicative of anti-angiogenic effects. Abnormal liver testing at baseline appeared to influence drug tolerability.

Keywords

Fostamatinib R406 R935788 Solid tumors Angiogenesis 

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Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA)  2013

Authors and Affiliations

  • Sook Ryun Park
    • 1
  • Giovanna Speranza
    • 1
  • Richard Piekarz
    • 1
  • John J. Wright
    • 1
  • Robert J. Kinders
    • 3
  • Lihua Wang
    • 3
  • Thomas Pfister
    • 3
  • Jane B. Trepel
    • 2
  • Min-Jung Lee
    • 2
  • Sylvia Alarcon
    • 2
  • Seth M. Steinberg
    • 2
  • Jerry Collins
    • 1
  • James H. Doroshow
    • 1
    • 2
  • Shivaani Kummar
    • 1
    • 2
  1. 1.Division of Cancer Treatment and DiagnosisNational Cancer InstituteBethesdaUSA
  2. 2.Center for Cancer ResearchNational Cancer InstituteBethesdaUSA
  3. 3.Applied/Developmental Research Directorate, SAIC-Frederick, Inc.Frederick National Laboratory for Cancer ResearchFrederickUSA

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