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

Publication ,  Journal Article
Rosen, LS; Lipton, L; Price, TJ; Belman, ND; Boccia, RV; Hurwitz, HI; Stephenson, JJ; Wirth, LJ; McCoy, S; Hei, Y-J; Hsu, C-P; Tebbutt, NC
Published in: BMC Cancer
May 16, 2013

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.

Duke Scholars

Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

May 16, 2013

Volume

13

Start / End Page

242

Location

England

Related Subject Headings

  • Young Adult
  • Oncology & Carcinogenesis
  • Oligonucleotides
  • Niacinamide
  • Neoplasms
  • Middle Aged
  • Male
  • Indoles
  • Humans
  • Gallbladder
 

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Rosen, L. S., Lipton, L., Price, T. J., Belman, N. D., Boccia, R. V., Hurwitz, H. I., … Tebbutt, N. C. (2013). The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors. BMC Cancer, 13, 242. https://doi.org/10.1186/1471-2407-13-242
Rosen, Lee S., Lara Lipton, Timothy J. Price, Neil D. Belman, Ralph V. Boccia, Herbert I. Hurwitz, Joe J. Stephenson, et al. “The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors.BMC Cancer 13 (May 16, 2013): 242. https://doi.org/10.1186/1471-2407-13-242.
Rosen LS, Lipton L, Price TJ, Belman ND, Boccia RV, Hurwitz HI, et al. The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors. BMC Cancer. 2013 May 16;13:242.
Rosen, Lee S., et al. “The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors.BMC Cancer, vol. 13, May 2013, p. 242. Pubmed, doi:10.1186/1471-2407-13-242.
Rosen LS, Lipton L, Price TJ, Belman ND, Boccia RV, Hurwitz HI, Stephenson JJ, Wirth LJ, McCoy S, Hei Y-J, Hsu C-P, Tebbutt NC. The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors. BMC Cancer. 2013 May 16;13:242.
Journal cover image

Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

May 16, 2013

Volume

13

Start / End Page

242

Location

England

Related Subject Headings

  • Young Adult
  • Oncology & Carcinogenesis
  • Oligonucleotides
  • Niacinamide
  • Neoplasms
  • Middle Aged
  • Male
  • Indoles
  • Humans
  • Gallbladder