title: Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer.
abstract: OBJECTIVE
  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 Following toxicity results for combination therapy in other trials, panitumumab was withdrawn from the study.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.
authors.affiliation: Department of Medical Oncology, Austin Health, Heidelberg, VIC, 3084, Australia, niall.tebbutt@ludwig.edu.au.
authors.forename: Niall
authors.initials: N
authors.lastname: Tebbutt
authors.forename: Dusan
authors.initials: D
authors.lastname: Kotasek
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: Lee S
authors.initials: LS
authors.lastname: Schwartzberg
authors.forename: Herbert
authors.initials: H
authors.lastname: Hurwitz
authors.forename: Joe
authors.initials: J
authors.lastname: Stephenson
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Warner
authors.forename: Lisa
authors.initials: L
authors.lastname: Chen
authors.forename: Cheng-Pang
authors.initials: CP
authors.lastname: Hsu
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D009841:Oligonucleotides; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077544:Panitumumab; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D007211:Indoles; D009841:Oligonucleotides; D009944:Organoplatinum Compounds; D009536:Niacinamide; D000077544:Panitumumab; C519562:imetelstat; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin