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

Publication ,  Journal Article
Tebbutt, N; Kotasek, D; Burris, HA; Schwartzberg, LS; Hurwitz, H; Stephenson, J; Warner, DJ; Chen, L; Hsu, C-P; Goldstein, D
Published in: Cancer Chemother Pharmacol
May 2015

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 Following toxicity results for combination therapy in other trials, panitumumab was withdrawn from the study.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.

Duke Scholars

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

May 2015

Volume

75

Issue

5

Start / End Page

993 / 1004

Location

Germany

Related Subject Headings

  • Young Adult
  • Panitumumab
  • Organoplatinum Compounds
  • Oncology & Carcinogenesis
  • Oligonucleotides
  • Niacinamide
  • Middle Aged
  • Male
  • Leucovorin
  • Indoles
 

Citation

APA
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ICMJE
MLA
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Tebbutt, N., Kotasek, D., Burris, H. A., Schwartzberg, L. S., Hurwitz, H., Stephenson, J., … Goldstein, D. (2015). Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. Cancer Chemother Pharmacol, 75(5), 993–1004. https://doi.org/10.1007/s00280-015-2694-y
Tebbutt, Niall, Dusan Kotasek, Howard A. Burris, Lee S. Schwartzberg, Herbert Hurwitz, Joe Stephenson, Douglas J. Warner, Lisa Chen, Cheng-Pang Hsu, and David Goldstein. “Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer.Cancer Chemother Pharmacol 75, no. 5 (May 2015): 993–1004. https://doi.org/10.1007/s00280-015-2694-y.
Tebbutt N, Kotasek D, Burris HA, Schwartzberg LS, Hurwitz H, Stephenson J, et al. Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. Cancer Chemother Pharmacol. 2015 May;75(5):993–1004.
Tebbutt, Niall, et al. “Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer.Cancer Chemother Pharmacol, vol. 75, no. 5, May 2015, pp. 993–1004. Pubmed, doi:10.1007/s00280-015-2694-y.
Tebbutt N, Kotasek D, Burris HA, Schwartzberg LS, Hurwitz H, Stephenson J, Warner DJ, Chen L, Hsu C-P, Goldstein D. Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. Cancer Chemother Pharmacol. 2015 May;75(5):993–1004.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

May 2015

Volume

75

Issue

5

Start / End Page

993 / 1004

Location

Germany

Related Subject Headings

  • Young Adult
  • Panitumumab
  • Organoplatinum Compounds
  • Oncology & Carcinogenesis
  • Oligonucleotides
  • Niacinamide
  • Middle Aged
  • Male
  • Leucovorin
  • Indoles