Show simple item record

dc.contributor.authorKotasek, D
dc.contributor.authorTebbutt, N
dc.contributor.authorDesai, J
dc.contributor.authorWelch, S
dc.contributor.authorSiu, LL
dc.contributor.authorMcCoy, S
dc.contributor.authorSun, Y-N
dc.contributor.authorJohnson, J
dc.contributor.authorAdewoye, AH
dc.contributor.authorPrice, T
dc.date.accessioned2021-02-12T00:24:17Z
dc.date.available2021-02-12T00:24:17Z
dc.date.issued2011-07-26
dc.identifierpii: 1471-2407-11-313
dc.identifier.citationKotasek, D., Tebbutt, N., Desai, J., Welch, S., Siu, L. L., McCoy, S., Sun, Y. -N., Johnson, J., Adewoye, A. H. & Price, T. (2011). Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study. BMC CANCER, 11 (1), https://doi.org/10.1186/1471-2407-11-313.
dc.identifier.issn1471-2407
dc.identifier.urihttp://hdl.handle.net/11343/260583
dc.description.abstractBACKGROUND: This phase 1b study assessed the maximum tolerated dose (MTD), safety, and pharmacokinetics of motesanib (a small-molecule antagonist of VEGF receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) administered once daily (QD) or twice daily (BID) in combination with erlotinib and gemcitabine in patients with solid tumors. METHODS: Patients received weekly intravenous gemcitabine (1000 mg/m2) and erlotinib (100 mg QD) alone (control cohort) or in combination with motesanib (50 mg QD, 75 mg BID, 125 mg QD, or 100 mg QD; cohorts 1-4); or erlotinib (150 mg QD) in combination with motesanib (100 or 125 mg QD; cohorts 5 and 6). RESULTS: Fifty-six patients were enrolled and received protocol-specified treatment. Dose-limiting toxicities occurred in 11 patients in cohorts 1 (n = 2), 2 (n = 4), 3 (n = 3), and 6 (n = 2). The MTD of motesanib in combination with gemcitabine and erlotinib was 100 mg QD. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. Frequently occurring motesanib-related adverse events included diarrhea (n = 19), nausea (n = 18), vomiting (n = 13), and fatigue (n = 12), which were mostly of worst grade < 3. The pharmacokinetics of motesanib was not markedly affected by coadministration of gemcitabine and erlotinib, or erlotinib alone. Erlotinib exposure, however, appeared lower after coadministration with gemcitabine and/or motesanib. Of 49 evaluable patients, 1 had a confirmed partial response and 26 had stable disease. CONCLUSIONS: Treatment with motesanib 100 mg QD plus erlotinib and gemcitabine was tolerable. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT01235416.
dc.languageEnglish
dc.publisherBMC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleSafety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study
dc.typeJournal Article
dc.identifier.doi10.1186/1471-2407-11-313
melbourne.affiliation.departmentSurgery (Austin & Northern Health)
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleBMC Cancer
melbourne.source.volume11
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1071179
melbourne.contributor.authorDesai, Jayesh
melbourne.contributor.authorTebbutt, Niall
dc.identifier.eissn1471-2407
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record