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

Niall Tebbutt, Dusan Kotasek, Howard A. Burris, Lee Schwartzberg, Herbert Hurwitz, Joe Stephenson, Douglas J. Warner, Lisa Chen, Cheng Pang Hsu, David Goldstein

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 Following toxicity results for combination therapy in other trials, panitumumab was withdrawn from the study.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

Original languageEnglish (US)
Pages (from-to)993-1004
Number of pages12
JournalCancer Chemotherapy and Pharmacology
Volume75
Issue number5
DOIs
StatePublished - May 1 2015

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Colorectal Neoplasms
Chemotherapy
Drug Therapy
Therapeutics
Molecules
Cholecystitis
Angiogenesis Inhibitors
Pharmacokinetics
imetelstat
panitumumab
Nausea
Vascular Endothelial Growth Factor A
Multicenter Studies
Fatigue
Toxicity
Labels
Diarrhea
Fatigue of materials
Hypertension
Safety

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. / Tebbutt, Niall; Kotasek, Dusan; Burris, Howard A.; Schwartzberg, Lee; Hurwitz, Herbert; Stephenson, Joe; Warner, Douglas J.; Chen, Lisa; Hsu, Cheng Pang; Goldstein, David.

In: Cancer Chemotherapy and Pharmacology, Vol. 75, No. 5, 01.05.2015, p. 993-1004.

Research output: Contribution to journalArticle

Tebbutt, N, Kotasek, D, Burris, HA, Schwartzberg, L, Hurwitz, H, Stephenson, J, Warner, DJ, Chen, L, Hsu, CP & Goldstein, D 2015, 'Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer', Cancer Chemotherapy and Pharmacology, vol. 75, no. 5, pp. 993-1004. https://doi.org/10.1007/s00280-015-2694-y
Tebbutt, Niall ; Kotasek, Dusan ; Burris, Howard A. ; Schwartzberg, Lee ; Hurwitz, Herbert ; Stephenson, Joe ; Warner, Douglas J. ; Chen, Lisa ; Hsu, Cheng Pang ; Goldstein, David. / Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. In: Cancer Chemotherapy and Pharmacology. 2015 ; Vol. 75, No. 5. pp. 993-1004.
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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.",
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T1 - Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer

AU - Tebbutt, Niall

AU - Kotasek, Dusan

AU - Burris, Howard A.

AU - Schwartzberg, Lee

AU - Hurwitz, Herbert

AU - Stephenson, Joe

AU - Warner, Douglas J.

AU - Chen, Lisa

AU - Hsu, Cheng Pang

AU - Goldstein, David

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

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