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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

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

Authors: 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, Niall C Tebbutt

Published in: BMC Cancer | Issue 1/2013

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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%.

Conclusions

Motesanib treatment was associated with increased gallbladder volume, decreased ejection fraction, biliary sludge, gallstone formation, and infrequent cholecystitis.

Trial registration

ClinicalTrials.gov NCT00448786
Appendix
Available only for authorised users
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Metadata
Title
The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors
Authors
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
Niall C Tebbutt
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-242

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