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Phase I study of pemetrexed with sorafenib in advanced solid tumors

PURPOSE: To determine if combination treatment with pemetrexed and sorafenib is safe and tolerable in patients with advanced solid tumors. RESULTS: Thirty-seven patients were enrolled and 36 patients were treated (24 in cohort A; 12 in cohort B). The cohort A dose schedule resulted in problematic cu...

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Autores principales: Poklepovic, Andrew, Gordon, Sarah, Shafer, Danielle A., Roberts, John D., Bose, Prithviraj, Geyer, Charles E., McGuire, William P., Tombes, Mary Beth, Shrader, Ellen, Strickler, Katie, Quigley, Maria, Wan, Wen, Kmieciak, Maciej, Massey, H. Davis, Booth, Laurence, Moran, Richard G., Dent, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5173162/
https://www.ncbi.nlm.nih.gov/pubmed/27213589
http://dx.doi.org/10.18632/oncotarget.9434
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author Poklepovic, Andrew
Gordon, Sarah
Shafer, Danielle A.
Roberts, John D.
Bose, Prithviraj
Geyer, Charles E.
McGuire, William P.
Tombes, Mary Beth
Shrader, Ellen
Strickler, Katie
Quigley, Maria
Wan, Wen
Kmieciak, Maciej
Massey, H. Davis
Booth, Laurence
Moran, Richard G.
Dent, Paul
author_facet Poklepovic, Andrew
Gordon, Sarah
Shafer, Danielle A.
Roberts, John D.
Bose, Prithviraj
Geyer, Charles E.
McGuire, William P.
Tombes, Mary Beth
Shrader, Ellen
Strickler, Katie
Quigley, Maria
Wan, Wen
Kmieciak, Maciej
Massey, H. Davis
Booth, Laurence
Moran, Richard G.
Dent, Paul
author_sort Poklepovic, Andrew
collection PubMed
description PURPOSE: To determine if combination treatment with pemetrexed and sorafenib is safe and tolerable in patients with advanced solid tumors. RESULTS: Thirty-seven patients were enrolled and 36 patients were treated (24 in cohort A; 12 in cohort B). The cohort A dose schedule resulted in problematic cumulative toxicity, while the cohort B dose schedule was found to be more tolerable. The maximum tolerated dose (MTD) was pemetrexed 750 mg/m(2) every 14 days with oral sorafenib 400 mg given twice daily on days 1–5. Because dosing delays and modifications were associated with the MTD, the recommended phase II dose was declared to be pemetrexed 500 mg/m(2) every 14 days with oral sorafenib 400 mg given twice daily on days 1–5. Thirty-three patients were evaluated for antitumor activity. One complete response and 4 partial responses were observed (15% overall response rate). Stable disease was seen in 15 patients (45%). Four patients had a continued response at 6 months, including 2 of 5 patients with triple-negative breast cancer. EXPERIMENTAL DESIGN: A phase I trial employing a standard 3 + 3 design was conducted in patients with advanced solid tumors. Cohort A involved a novel dose escalation schema exploring doses of pemetrexed every 14 days with continuous sorafenib. Cohort B involved a modified schedule of sorafenib dosing on days 1–5 of each 14-day pemetrexed cycle. Radiographic assessments were conducted every 8 weeks. CONCLUSIONS: Pemetrexed and intermittent sorafenib therapy is a safe and tolerable combination for patients, with promising activity seen in patients with breast cancer.
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spelling pubmed-51731622016-12-23 Phase I study of pemetrexed with sorafenib in advanced solid tumors Poklepovic, Andrew Gordon, Sarah Shafer, Danielle A. Roberts, John D. Bose, Prithviraj Geyer, Charles E. McGuire, William P. Tombes, Mary Beth Shrader, Ellen Strickler, Katie Quigley, Maria Wan, Wen Kmieciak, Maciej Massey, H. Davis Booth, Laurence Moran, Richard G. Dent, Paul Oncotarget Clinical Research Paper PURPOSE: To determine if combination treatment with pemetrexed and sorafenib is safe and tolerable in patients with advanced solid tumors. RESULTS: Thirty-seven patients were enrolled and 36 patients were treated (24 in cohort A; 12 in cohort B). The cohort A dose schedule resulted in problematic cumulative toxicity, while the cohort B dose schedule was found to be more tolerable. The maximum tolerated dose (MTD) was pemetrexed 750 mg/m(2) every 14 days with oral sorafenib 400 mg given twice daily on days 1–5. Because dosing delays and modifications were associated with the MTD, the recommended phase II dose was declared to be pemetrexed 500 mg/m(2) every 14 days with oral sorafenib 400 mg given twice daily on days 1–5. Thirty-three patients were evaluated for antitumor activity. One complete response and 4 partial responses were observed (15% overall response rate). Stable disease was seen in 15 patients (45%). Four patients had a continued response at 6 months, including 2 of 5 patients with triple-negative breast cancer. EXPERIMENTAL DESIGN: A phase I trial employing a standard 3 + 3 design was conducted in patients with advanced solid tumors. Cohort A involved a novel dose escalation schema exploring doses of pemetrexed every 14 days with continuous sorafenib. Cohort B involved a modified schedule of sorafenib dosing on days 1–5 of each 14-day pemetrexed cycle. Radiographic assessments were conducted every 8 weeks. CONCLUSIONS: Pemetrexed and intermittent sorafenib therapy is a safe and tolerable combination for patients, with promising activity seen in patients with breast cancer. Impact Journals LLC 2016-05-18 /pmc/articles/PMC5173162/ /pubmed/27213589 http://dx.doi.org/10.18632/oncotarget.9434 Text en Copyright: © 2016 Poklepovic et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Clinical Research Paper
Poklepovic, Andrew
Gordon, Sarah
Shafer, Danielle A.
Roberts, John D.
Bose, Prithviraj
Geyer, Charles E.
McGuire, William P.
Tombes, Mary Beth
Shrader, Ellen
Strickler, Katie
Quigley, Maria
Wan, Wen
Kmieciak, Maciej
Massey, H. Davis
Booth, Laurence
Moran, Richard G.
Dent, Paul
Phase I study of pemetrexed with sorafenib in advanced solid tumors
title Phase I study of pemetrexed with sorafenib in advanced solid tumors
title_full Phase I study of pemetrexed with sorafenib in advanced solid tumors
title_fullStr Phase I study of pemetrexed with sorafenib in advanced solid tumors
title_full_unstemmed Phase I study of pemetrexed with sorafenib in advanced solid tumors
title_short Phase I study of pemetrexed with sorafenib in advanced solid tumors
title_sort phase i study of pemetrexed with sorafenib in advanced solid tumors
topic Clinical Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5173162/
https://www.ncbi.nlm.nih.gov/pubmed/27213589
http://dx.doi.org/10.18632/oncotarget.9434
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