Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/71780
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Type: | Journal article |
Title: | Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study |
Author: | Kotasek, D. Tebbutt, N. Desai, J. Welch, S. Siu, L. McCoy, S. Sun, Y. Johnson, J. Adewoye, A. Price, T. |
Citation: | BMC Cancer, 2011; 11(1):313-1-313-13 |
Publisher: | BioMed Central Ltd. |
Issue Date: | 2011 |
ISSN: | 1471-2407 1471-2407 |
Statement of Responsibility: | Dusan Kotasek, Niall Tebbutt, Jayesh Desai, Stephen Welch, Lillian L Siu, Sheryl McCoy, Yu-Nien Sun, Jessica Johnson, Adeboye H Adewoye and Timothy Price |
Abstract: | Background: 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. |
Keywords: | Humans Neoplasms Venous Thrombosis Hypertension Nausea Vomiting Niacinamide Indoles Quinazolines Deoxycytidine Oligonucleotides Antineoplastic Combined Chemotherapy Protocols Metabolic Clearance Rate Treatment Outcome Drug Administration Schedule Area Under Curve Cohort Studies Dose-Response Relationship, Drug Adult Aged Middle Aged Female Male Young Adult Erlotinib Hydrochloride Gemcitabine |
Rights: | © 2011 Kotasek 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: | 10.1186/1471-2407-11-313 |
Published version: | http://dx.doi.org/10.1186/1471-2407-11-313 |
Appears in Collections: | Aurora harvest Medicine publications |
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hdl_71780.pdf | Published version | 506.97 kB | Adobe PDF | View/Open |
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