The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors

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dc.contributor.authorRosen, L.
dc.contributor.authorLipton, L.
dc.contributor.authorPrice, T.
dc.contributor.authorBelman, N.
dc.contributor.authorBoccia, R.
dc.contributor.authorHurwitz, H.
dc.contributor.authorStephenson Jr, J.
dc.contributor.authorWirth, L.
dc.contributor.authorMcCoy, S.
dc.contributor.authorHei, Y.
dc.contributor.authorHsu, C.
dc.contributor.authorTebbutt, N.
dc.date.issued2013
dc.descriptionExtent: 11 p.
dc.description.abstractBACKGROUND: Gallbladder toxicity, including cholecystitis, has been reported with motesanib, an orally administered small-molecule antagonist of VEGFRs 1, 2 and 3; PDGFR; and Kit. We assessed effects of motesanib on gallbladder size and function. METHODS: Patients with advanced metastatic solid tumors ineligible for or progressing on standard-of-care therapies with no history of cholecystitis or biliary disease were randomized 2:1:1 to receive motesanib 125 mg once daily (Arm A); 75 mg twice daily (BID), 14-days-on/7-days-off (Arm B); or 75 mg BID, 5-days-on/2-days-off (Arm C). Primary endpoints were mean change from baseline in gallbladder size (volume by ultrasound; independent review) and function (ejection fraction by CCK-HIDA; investigator assessment). RESULTS: Forty-nine patients received ≥1 dose of motesanib (Arms A/B/C, n = 25/12/12). Across all patients, gallbladder volume increased by a mean 22.2 cc (from 38.6 cc at baseline) and ejection fraction decreased by a mean 19.2% (from 61.3% at baseline) during treatment. Changes were similar across arms and appeared reversible after treatment discontinuation. Three patients had cholecystitis (grades 1, 2, 3, n = 1 each) that resolved after treatment discontinuation, one patient developed grade 3 acute cholecystitis requiring cholecystectomy, and two patients had other notable grade 1 gallbladder disorders (gallbladder wall thickening, gallbladder dysfunction) (all in Arm A). Two patients developed de novo gallstones during treatment. Twelve patients had right upper quadrant pain (Arms A/B/C, n = 8/1/3). The incidence of biliary “sludge” in Arms A/B/C was 39%/36%/27%. CONCLUSION: Motesanib treatment was associated with increased gallbladder volume, decreased ejection fraction, biliary sludge, gallstone formation, and infrequent cholecystitis. Trial registration: ClinicalTrials.gov NCT00448786
dc.description.statementofresponsibilityLee S. Rosen, Lara Lipton, Timothy J. Price, Neil D. Belman, Ralph V. Boccia, Herbert I. Hurwitz, Joe J. Stephenson Jr., Lori J. Wirth, Sheryl McCoy, Yong-jiang Hei, Cheng-Pang Hsu and Niall C. Tebbutt
dc.identifier.citationBMC Cancer, 2013; 13(242):1-11
dc.identifier.doi10.1186/1471-2407-13-242
dc.identifier.issn1471-2407
dc.identifier.issn1471-2407
dc.identifier.orcidPrice, T. [0000-0002-3922-2693]
dc.identifier.urihttp://hdl.handle.net/2440/79421
dc.language.isoen
dc.publisherBioMed Central Ltd.
dc.rights© 2013 Rosen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttps://doi.org/10.1186/1471-2407-13-242
dc.subjectGallbladder
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectNiacinamide
dc.subjectIndoles
dc.subjectOligonucleotides
dc.subjectAntineoplastic Agents
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.titleThe effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors
dc.typeJournal article
pubs.publication-statusPublished

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