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Cancer Chemotherapy and Pharmacology

, Volume 75, Issue 5, pp 993–1004 | Cite as

Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer

  • Niall TebbuttEmail author
  • Dusan Kotasek
  • Howard A. Burris
  • Lee S. Schwartzberg
  • Herbert Hurwitz
  • Joe Stephenson
  • Douglas J. Warner
  • Lisa Chen
  • Cheng-Pang Hsu
  • David Goldstein
Original Article

Abstract

Purpose

This study assessed the safety, efficacy, and pharmacokinetics of motesanib, a multitargeted small molecule angiogenesis inhibitor, with and without panitumumab, in combination with FOLFIRI or FOLFOX in patients with metastatic colorectal cancer (mCRC).

Methods

This open-label, phase 1b, two-part, multicenter study in patients with mCRC and ≤1 prior treatment evaluated escalating doses (50, 75, 100, or 125 mg QD, 75 mg BID) of motesanib with panitumumab and chemotherapy (Part 1) and the target dose of motesanib with chemotherapy (Part 2).

Results

At 17 sites in the USA and Australia, 119 patients were enrolled between December 2004 and February 2010. In Part 1 [motesanib plus panitumumab/FOLFIRI (n = 36) or plus panitumumab/FOLFOX (n = 17)], all motesanib doses tested were tolerated and 125 mg QD was deemed the target dose. Following toxicity results for combination therapy in other trials, panitumumab was withdrawn from the study. Part 2 evaluated motesanib 125 mg with chemotherapy [FOLFIRI (n = 37); FOLFOX (n = 29)]. The primary endpoint, objective response rate in patients with measurable disease by RECIST, was 20 % overall and was higher among patients receiving first-line (27 % overall; FOLFOX, 24 %; FOLFIRI, 27 %) compared with second-line therapy (14 % overall; FOLFOX, 0 %; FOLFIRI, 20 %). The most common adverse events were diarrhea, nausea, fatigue, and hypertension. We observed a low rate of cholecystitis [3 of 119 (2.5 %)], a known adverse event of motesanib and other small molecule VEGF inhibitors.

Conclusions

Motesanib 125 mg QD in combination with FOLFIRI or FOLFOX chemotherapy was tolerated and demonstrated modest efficacy in first-/second-line mCRC.

Keywords

Anti-angiogenic Targeted agent Metastatic colorectal cancer Dose-escalation Motesanib Panitumumab 

Notes

Acknowledgments

This work was sponsored by Amgen Inc. The authors would like to thank Yining Ye for statistical support; Bethlyn Sloey, Shubhada Kulkarni, and Bernd Bruenner, all of Amgen Inc., for their contribution to PK sample and data analysis; and Wanda Krall, Ph.D., whose work was funded by Amgen Inc., for assistance in the preparation of this manuscript.

Supplementary material

280_2015_2694_MOESM1_ESM.docx (250 kb)
Supplementary material 1 (DOCX 250 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Niall Tebbutt
    • 1
    Email author
  • Dusan Kotasek
    • 2
  • Howard A. Burris
    • 3
  • Lee S. Schwartzberg
    • 4
  • Herbert Hurwitz
    • 5
  • Joe Stephenson
    • 6
  • Douglas J. Warner
    • 7
  • Lisa Chen
    • 7
  • Cheng-Pang Hsu
    • 7
  • David Goldstein
    • 8
  1. 1.Department of Medical OncologyAustin HealthHeidelbergAustralia
  2. 2.Ashford Cancer CentreAshfordAustralia
  3. 3.Sarah Cannon Research InstituteNashvilleUSA
  4. 4.The West ClinicMemphisUSA
  5. 5.Duke University Medical CenterDurhamUSA
  6. 6.Cancer Center of the CarolinasGreenvilleUSA
  7. 7.Amgen Inc.Thousand OaksUSA
  8. 8.Prince of Wales Clinical School, University of New South WalesPrince of Wales HospitalSydneyAustralia

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