Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study
<p>Abstract</p> <p>Background</p> <p>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...
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| Format: | Article |
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BMC
2011-07-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/11/313 |
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| author | Sun Yu-Nien McCoy Sheryl Siu Lillian L Welch Stephen Desai Jayesh Tebbutt Niall Kotasek Dusan Johnson Jessica Adewoye Adeboye H Price Timothy |
| author_facet | Sun Yu-Nien McCoy Sheryl Siu Lillian L Welch Stephen Desai Jayesh Tebbutt Niall Kotasek Dusan Johnson Jessica Adewoye Adeboye H Price Timothy |
| author_sort | Sun Yu-Nien |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>Patients received weekly intravenous gemcitabine (1000 mg/m<sup>2</sup>) 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).</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>Treatment with motesanib 100 mg QD plus erlotinib and gemcitabine was tolerable. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01235416">NCT01235416</a></p> |
| first_indexed | 2024-12-12T12:11:19Z |
| format | Article |
| id | doaj.art-0f4cd09bfde34a258b2bc0068c98dce9 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-12T12:11:19Z |
| publishDate | 2011-07-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj.art-0f4cd09bfde34a258b2bc0068c98dce92022-12-22T00:24:52ZengBMCBMC Cancer1471-24072011-07-0111131310.1186/1471-2407-11-313Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b studySun Yu-NienMcCoy SherylSiu Lillian LWelch StephenDesai JayeshTebbutt NiallKotasek DusanJohnson JessicaAdewoye Adeboye HPrice Timothy<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>Patients received weekly intravenous gemcitabine (1000 mg/m<sup>2</sup>) 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).</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>Treatment with motesanib 100 mg QD plus erlotinib and gemcitabine was tolerable. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01235416">NCT01235416</a></p>http://www.biomedcentral.com/1471-2407/11/313 |
| spellingShingle | Sun Yu-Nien McCoy Sheryl Siu Lillian L Welch Stephen Desai Jayesh Tebbutt Niall Kotasek Dusan Johnson Jessica Adewoye Adeboye H Price Timothy Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study BMC Cancer |
| title | Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study |
| title_full | Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study |
| title_fullStr | Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study |
| title_full_unstemmed | Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study |
| title_short | Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study |
| title_sort | safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors a phase 1b study |
| url | http://www.biomedcentral.com/1471-2407/11/313 |
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