Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/79421
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Type: | Journal article |
Title: | The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors |
Author: | Rosen, L. Lipton, L. Price, T. Belman, N. Boccia, R. Hurwitz, H. Stephenson Jr, J. Wirth, L. McCoy, S. Hei, Y. Hsu, C. Tebbutt, N. |
Citation: | BMC Cancer, 2013; 13(242):1-11 |
Publisher: | BioMed Central Ltd. |
Issue Date: | 2013 |
ISSN: | 1471-2407 1471-2407 |
Statement of Responsibility: | Lee 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 |
Abstract: | BACKGROUND: 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 |
Keywords: | Gallbladder Humans Neoplasms Niacinamide Indoles Oligonucleotides Antineoplastic Agents Adult Aged Aged, 80 and over Middle Aged Female Male Young Adult |
Description: | Extent: 11 p. |
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. |
DOI: | 10.1186/1471-2407-13-242 |
Published version: | http://dx.doi.org/10.1186/1471-2407-13-242 |
Appears in Collections: | Aurora harvest Medicine publications |
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hdl_79421.pdf | Published version | 386.51 kB | Adobe PDF | View/Open |
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